Method and system for control of a patient&#39;s body temperature by way of a transluminally insertable heat exchange catheter

ABSTRACT

Methods and apparatuses for temperature modification of a patient, or selected regions thereof, including an induced state of hypothermia. The temperature modification is accomplished using an in-dwelling heat exchange catheter within which a fluid heat exchange medium circulates. A heat exchange cassette of any one of several disclosed variations is attached to the circulatory conduits of the catheter, the heat exchange cassette being sized to engage a cavity within one of various described re-usable control units. The control units include a heater/cooler device, a user input device, and a processor connected to receive input from various sensors around the body and the system. The heater/cooler device may be thermoelectric to enable both heating and cooling based on polarity. A temperature control scheme for ramping the body temperature up or down without overshoot is provided. The disposable heat exchange cassettes may include an integral pump head that engages with a pump drive mechanism within the re-usable control unit. More than one control unit may be provided to receive the same heat exchange cassette so that, for example, a large capacity control unit can be used initially, and a smaller, battery-powered unit can be substituted once the patient reaches the desired target temperature.

RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.09/563,946, filed May 2, 2000 and claims the benefit of priority under35 U.S.C. §119(e) of U.S. Provisional Application Ser. No. 60/185,561,filed Feb. 28, 2000 and U.S. Provisional Application Ser. No.60/219,922, filed Jul. 21, 2000.

FIELD OF THE INVENTION

The present invention relates generally to medical devices and methodsand, more particularly, to a programmable, microprocessor basedcontroller and method for controlling the temperature and flow of athermal exchange fluid that is circulated through a heat exchangecatheter inserted into a patient's body for the purpose or cooling orwarming at least a portion of the patient's body.

BACKGROUND OF THE INVENTION

Under ordinary circumstances, the thermoregulatory mechanisms of ahealthy human body serve to maintain the body at a constant temperatureof about 37° C. (98.6° F.), a condition sometimes referred to asnormothermia. To maintain normothermia, the thermoregulatory mechanismsact so that heat lost from the person's body is replaced by the sameamount of heat generated by metabolic activity within the body. Forvarious reasons such as extreme environmental exposure to a coldenvironment or loss of thermoregulatory ability as a result of diseaseor anesthesia, a person may develop a body temperature that is belownormal, a condition known as hypothermia. A person may develop acondition that is above normothermia, a condition known as hyperthermia,as a result of extreme exposure to a hot environment, or malfunctioningthermoregulatory mechanisms, the latter being a condition sometimescalled malignant hyperthermia. The body may also establish a set pointtemperature (that is, the temperature which the body's thermoregulatorymechanisms function to maintain) that is above normothermia, a conditionusually referred to as fever. The present invention addresses all ofthese situations.

Accidental hypothermia is generally a dangerous condition that may evenbe life threatening, and requires treatment. If severe, for examplewhere the body temperature drops below 30° C., hypothermia may haveserious consequences such as cardiac arrhythmias, inability of the bloodto clot normally, or interference with normal metabolism. If the periodof hypothermia is extensive, the patient may even experience impairedimmune response and increased incidence of infection.

Simple methods for treating accidental hypothermia have been known sincevery early times. Such methods include wrapping the patient in blankets,administering warm fluids by mouth, and immersing the patient in a warmwater bath. If the hypothermia is not too severe, these methods may beeffective. However, wrapping a patient in a blanket depends on theability of the patient's own body to generate heat to re-warm the body.Administering warm fluids by mouth relies on the patient's ability,toswallow, and is limited in the temperature of the liquid consumed andthe amount of fluid that may be administered in a limited period oftime. Immersing a patient in warm water is often impractical,particularly if the patient is simultaneously undergoing surgery or someother medical procedure.

More recently, hypothermia may be treated in a more complex fashion.Heated warming blankets may be applied to a patient or warming lampsthat apply heat to the skin of the patient may be used. Heat applied tothe patient's skin, however, has to transmit through the skin byconduction or radiation which may be slow and inefficient, and the bloodflow to the skin may be shut down by the body's thermoregulatoryresponse, and thus, even if the skin is warmed, such mechanisms may beineffective in providing heat to the core of the patient's body. Whenbreathing gases are administered to a patient, for example a patientunder anesthesia, the breathing gases may be warmed. This provides heatrelatively fast to the patient, but the amount of heat that can beadministered without injuring the patient's lungs is very limited. Analternative method of warming a hypothermic patient involves infusing ahot liquid into the patient via an IV infusion, but this is limited bythe amount of liquid that can be infused and the temperature of theliquid.

In extreme situations, a very invasive method may be employed to controlhypothermia. Shunts may be placed into the patient to direct blood fromthe patient through an external machine such as a cardiopulmonaryby-pass (CPB) machine which includes a heater. In this way, the bloodmay be removed from the patient, heated externally, and pumped back intothe patient. Such extreme measures have obvious advantages as toeffectiveness, but also obvious drawbacks as to invasiveness. Thepumping of blood through an external circuit that treats the blood isgenerally quite damaging to the blood, and the procedure is onlypossible in a hospital setting with highly trained personnel operatingthe equipment.

Accidental hyperthermia may also result from various conditions. Wherethe normal thermoregulatory ability of the body is lost, because ofdisease or anesthesia, run-away hyperthermia, also known as malignanthyperthermia, may result. The body may also set a higher than normal setpoint resulting in fever which is a type of hyperthermia. Likehypothermia, accidental hyperthermia is a serious condition that maysometimes be fatal. In particular, hyperthermia has been found to beneurodestructive, both in itself or in conjunction with other healthproblems such as traumatic brain injury or stroke, where a bodytemperature in excess of normal has been shown to result in dramaticallyworse outcomes, even death.

As with hypothermia, when the condition is not too severe, simplemethods for treating the condition exist, such as cold water baths andcooling blankets, or antipyretic drugs such as aspirin or acetominophen,and for the more extreme cases, more effective but complex and invasivemeans such as cooled breathing gases, cold infusions, and blood cooledduring CPB also exist. These, however, are subject to the limitationsand complications as described above in connection with hypothermia.

Although both hypothermia and hyperthermia may be harmful and requiretreatment in some case, in other cases hyperthermia, and especiallyhypothermia, may be therapeutic or otherwise advantageous, and thereforemay be intentionally induced. For example, periods of cardiac arrest orcardiac insufficiency in heart surgery result in insufficient blood tothe brain and spinal cord, and thus can produce brain damage or othernerve damage. Hypothermia is recognized in the medical community as anaccepted neuroprotectant and therefore a patient is often kept in astate of induced hypothermia. Hypothermia also has similar advantageousprotective ability for treating or minimizing the adverse effects ofcertain neurological diseases or disorders such as head trauma, spinaltrauma and hemorrhagic or ischemic stroke. Therefore it is sometimesdesirable to induce whole-body or regional hypothermia for the purposeof facilitating or minimizing adverse effects of certain surgical orinterventional procedures such as open heart surgery, aneurysm repairsurgeries, endovascular aneurysm repair procedures, spinal surgeries, orother surgeries where blood flow to the brain, spinal cord or vitalorgans may be interrupted or compromised. Hypothermia has even beenfound to be advantageous to protect cardiac muscle tissue after amyocardial infarct (MI).

Current methods of attempting to induce hypothermia generally involveconstant surface cooling, by cooling blanket or by alcohol or ice waterrubs. However, such cooling methods are extremely cumbersome, andgenerally ineffective to cool the body's core. The body's response tocold alcohol or ice water applied to the surface is to shut down thecirculation of blood through the capillary beds, and to the surface ofthe body generally, and thus to prevent the cold surface from coolingthe core. If the surface cooling works at all, it does so very slowly.There is also an inability to precisely control the temperature of thepatient by this method.

If the patient is in a surgical setting, the patient may be anesthetizedand cooled by CPB as described above. Generally, however, this is onlyavailable in the most extreme situations involving a full surgical teamand full surgical suite, and importantly, is only available for a shortperiod of time because of the damage to the blood caused by pumping.Generally surgeons do not wish to pump the blood for periods longer than4 hours, and in the case of stroke or traumatic brain damage, it may bedesirable to induce hypothermia for longer than a full day. Because ofthe direct control of the temperature of a large amount of blood, thismethod allows fairly precise control of the patient's temperature.However, it is this very external manipulation of large amounts of thepatient's blood that makes long term use of this procedure veryundesirable.

Means for effectively adding heat to the core of the body that do notinvolve pumping the blood with an external, mechanical pump have beensuggested. For example, a method of treating hypothermia or hyperthermiaby means of a heat exchange catheter placed in the bloodstream of apatient was described in U.S. Pat. No. 5,486,208 to Ginsburg, thecomplete disclosure of which is incorporated herein by reference. Meansof controlling the temperature of a patient by controlling such a systemis disclosed in U.S. Pat. No. 5,837,003, also to Ginsburg, the completedisclosure of which is incorporated herein by reference. A furthersystem for such controlled intervascular temperature control isdisclosed in publication WO 00/10494 to Ginsburg et al., the completedisclosure of which is incorporated herein by reference. Those patentsand publication disclose a method of treating or inducing hypothermia byinserting a heat exchange catheter having a heat exchange area includinga balloon with heat exchange fins into the bloodstream of a patient, andcirculating heat exchange fluid through the balloon while the balloon isin contact with the blood to add or remove heat from the bloodstream.(As used herein, a balloon is a structure that is readily inflated underpressure and collapsed under vacuum.)

A number of catheter systems for cooling tissue adjacent the catheter orregulating the temperature of the catheter using the temperature offluid circulating within the catheter are shown in the published art.Some such catheters rely on a reservoir or similar tank for a supply ofheat exchange fluid. For example, U.S. Pat. No. 3,425,419 to Dato, U.S.Pat. No. 5,423,811 to Imran et al., U.S. Pat. No. 5,733,319 to Neilson,et al., U.S. Pat. No. 6,019,783 to Phillips, et al., and. U.S. Pat. No.5,624,392 to Saab disclose catheters with circulating heat exchangefluid from a tank or reservoir. For such systems that involve a catheterplaced in the bloodstream, however, difficulties arise in sterilizingthe fluid source between uses and rapidly changing the temperature of alarge volume of fluid having a significant thermal mass.

For the foregoing reasons, there is a need for a rapid and effectivemeans to add or remove heat from the fluid supply for a catheter used tocontrol the body temperature of a patient in an effective and efficientmanner, while avoiding the inadequacies of the prior art methods. Inparticular, a fluid source that rapidly, efficiently and controllablyregulates a disposable source of fluid based on feedback from thetemperature of the patient or target tissue within the patient would bea great advantage.

SUMMARY OF THE INVENTION

The present invention avoids many of the problems of the prior art byproviding an improved system to control the heating and/or cooling of acatheter with a body. The system generally includes a control unitexterior to body, a number of conduits extending from the control unit,and a heat transfer catheter in communication with the control unit viathe conduits. The control unit modulates the temperature of a heattransfer region on the catheter using an advantageous controlmethodology to avoid over-shooting a target temperature. The catheterand conduits preferably define a fluid circulation path, wherein thecontrol unit modulates the temperature of the heat transfer region byadjusting the temperature of a heat transfer fluid within thecirculation path. Desirably, the control unit defines a cavity and theconduits are connected to a cassette that fits within the cavity, thecassette having an external heat exchanger through which the heatexchange fluid flows.

In one aspect of the present invention, a controller for controlling thetemperature and flow of heat exchange fluid within a circuit isprovided. The circuit is of a type that includes a heat exchangecatheter, an external heat exchanger, and a pump for flowing heatexchange fluid through the circuit. The controller includes a heatand/or cold generating element in thermal contact with the external heatexchanger containing the heat exchange fluid. A patient sensor ispositioned and configured to generate a signal representing abiophysical condition of the patient. The microprocessor in thecontroller receives the signal from the patient sensor and responds bycontrolling the generating element. The control unit further includes amechanical drive unit for activating the pump contained in the circuit,and a safety sensor for detecting a fluid parameter in the circuit togenerate a safety signal representative of the presence or absence ofthe fluid parameter. The safety signal is transmitted to themicroprocessor that responds by controlling the operation of the pump.The sensor may be a bubble detector, and the fluid parameter is gasentrained in the heat exchange fluid. Alternatively, the circuit furthercomprises a reservoir, and the sensor is a fluid level detector fordetecting a low fluid level in the reservoir.

In a still further aspect of the present invention, a heat transfercatheter flow system comprises a heat transfer medium circulation loopincluding a transfer catheter, a heat transfer unit, and conduitscoupled to the heat transfer catheter and heat transfer unit that enablecirculation of the heat transfer medium therebetween. The system furtherincludes a pump head in contact with heat transfer medium within thecirculation loop for circulating the medium through the loop. A cassetteincluding a heat transfer unit and the pump head mates with a controllerhousing a control circuit and a pump motor so that the pump head engagesthe pump motor. An electronic feedback loop that detects back-torqueexperienced by the pump motor provides feedback to a control circuitthat in turn controls the speed of the pump motor.

In another aspect, the present invention provides a controller forcontrolling the temperature and flow of heat exchange fluid within acircuit of the type that has a heat exchange catheter, an external heatexchanger, and a pump for flowing heat exchange fluid through thecircuit. The controller includes a heat and/or cold generating elementin thermal contact with the external heat exchanger. A mechanical driveunit activates the pump contained in the circuit to pump the heatexchange fluid. The controller includes a microprocessor connected tocontrol both the generating element and the mechanical drive unit. Asafety system is provided for detecting problems in the circuit. Thesafety system includes a plurality of sensors that generate signalsindicative of respective parameters of the system and/or patient. Thesignals are transmitted to the microprocessor that responds bycontrolling the operation of the generating element and the mechanicaldrive unit. In one embodiment, the safety system includes a sensor fordetecting the fluid level within the circuit. In a further embodiment,the safety system includes a sensor for detecting the temperature of alocation within the patient, and further may include a redundant sensorfor detecting the temperature of a location within the patient wherein amicroprocessor is responsive to a difference in the two sensed patienttemperatures. Furthermore, the safety system may include sensors fordetecting bubbles within the circuit, detecting the operating status ofthe generating element, or detecting the operating status of themechanical drive unit.

In one embodiment of the invention, a heat transfer catheter systemincludes a heat transfer catheter, a heat transfer unit, and conduitscoupling the two elements and enabling circulation of heat transfermedium therebetween. The heat transfer unit defines a flow channelbetween opposite sidewalls, one of the sidewalls being relatively thinand flexible and providing minimal thermal insulation, while theopposite sidewall is relatively non-flexible so as to provide structuralsupport to the heat transfer unit. The system may include a controllerhaving a cavity for receiving the heat transfer unit and a heat and/orcold generating element therein positioned adjacent the flexiblesidewall when the heat transfer unit is inserted within the cavity. Thecavity may be sized such that outward expansion of the flexible sidewallupon flow of heat exchange medium through the flow channel causes theheat transfer unit to become compressively retained within the cavity.Desirably, the flexible sidewall attaches to the opposite sidewall botharound their respective edges and along a series of lines within theedges such that the flow channel defines a serpentine path.

The present invention also provides a method of regulating thetemperature of patient, comprising the steps of:

providing a heat exchange catheter system including a heat exchangecatheter having a fluid path therethrough, a pair of conduits fluidlyconnected to the heat exchange catheter, and an external heat exchangerconnected via the conduits to circulate heat exchange medium through theexchange catheter;

providing a first controller adapted to couple to the external heatexchanger of the heat exchange catheter system, the first controllerincluding a heat and/or cold generating element therein for exchangingheat at a first rate with the heat exchange medium within the externalheat exchanger;

providing a second controller adapted to couple to the external heatexchanger of the heat exchange catheter system, the second controllerincluding a heat and/or cold generating element therein for exchangingheat at a second rate with the heat exchange medium within the externalheat exchanger;

coupling the heat exchange catheter system with the first controller;

inserting the heat exchange catheter into the patient;

regulating the temperature of the patient by exchanging heat at thefirst rate between the generating element of the first controller andthe external heat exchanger;

de-coupling the heat exchange catheter system from the first controller;

coupling the heat exchange catheter system with the second controller;and

regulating the temperature of the patient by exchanging heat at thesecond rate between the generating element of the second controller andthe external heat exchanger.

The method may include performing a therapeutic or diagnostic procedureon the patient between the steps of de-coupling the heat exchangecatheter system from the first controller and the step of coupling theheat exchange catheter system with the second controller. Indeed, thefirst controller and the second controller may be the same physicaldevice.

In a still further method of the present invention, the rate of changeof a patient's body temperature is controlled using a heat transfercatheter and associated controller. The transfer catheter has a heattransfer region thereon, and the controller is placed in communicationwith the catheter via conduits. The controller is adapted to elevate ordepress the temperature of the catheter heat transfer region relative tothe body temperature. The patient's body temperature within a bodycavity or in another location is sensed, while the temperature of theheat transfer region is determined. A target temperature is thenselected. The target temperature may be different than the bodytemperature, or may be the same if maintenance of normal patienttemperature is the goal. A ramp rate equal to the time rate of change oftemperature from the body temperature to the target temperature isselected. The temperature of the transfer region of the catheter basedon the ramp rate is set. The method includes monitoring the temperaturedifferential between the target temperature and the body temperature,and reducing the ramp rate when the temperature differential reducesbelow a predetermined threshold. Desirably, the heat transfer catheterand conduits defined a fluid circulation path therethrough, wherein thestep of setting the temperature of the catheter heat transfer regioncomprises setting the temperature of a circulating fluid within thecirculation path. Preferably, the step of determining the temperature ofthe catheter heat transfer region comprises directly or indirectlysensing the temperature of the circulating fluid. A comparison may bemade between the target temperature and the temperature of thecirculating fluid, which is then used to adjust the temperature of thecirculating fluid.

In one aspect of the invention, the reservoir section is provided with ameans to detect the fluid level in the reservoir and comprises at leastone prism mounted within the reservoir section adjacent the inside of arelatively transparent window or wall portion in the reservoir, and atleast one optical beam source and at least one optical beam sensormounted on the reusable control unit adjacent the outside of the window.In one specific embodiment, the fluid level detector comprises a prismmounted in the reservoir, a light beam source and a light beam sensor.The prism has a diffraction surface and the light beam source directs alight beam against that surface. The prism is configured so that whenthe diffraction surface is in contact with air, the light beam isreflected to impinge on the light beam sensor and the sensor generates asignal. Likewise, when the diffraction surface is in contact with fluid,the light beam does not reflect to the sensor and the sensor does notgenerate a signal.

In operation, a light beam is directed through the reservoir section andagainst the prism at a particular point along its angled length. Thesensor is located to detect the presence or absence of a reflected beam.As long as the fluid reservoir remains full and the fluid level is at apre-determined elevation above the point of impingement of the lightbeam, the diffraction surface of the prism at that point is in contactwith the fluid. Therefore, the light beam directed at the prism travelsthrough the prism and, upon reaching the diffraction surface, isreflected such that the sensor does not observe a reflected beam. If thefluid falls below the pre-determined elevation, the diffraction surfaceof the prism at the point where the beam impinges on it will no longerbe in contact with the fluid and will be in contact with air instead.Air has a different index of refraction than the index of refraction ofthe fluid. Accordingly, upon reaching the diffraction surface, thereflected beam will no longer reflect out to the same point, and isreflected in such a manner that it impinges upon the sensor, which willthen observe a reflected beam.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a patient undergoing treatment using asystem in accordance with the present invention;

FIG. 2 is a schematic illustration of a disposable heat exchangecassette attached to a heat exchange catheter and an external fluidsource, and positioned for insertion into a suitable opening in are-usable control unit of the present invention,

FIGS. 3A-3B together show a flowchart of a control scheme of the heatexchange system of the present invention;

FIG. 4 is a graph of the sensed temperature of a target tissue or bodyfluid over time under the influence of the control scheme of FIGS.3A-3B;

FIG. 5A is a perspective view of an exemplary re-usable control unit ofthe present invention;

FIG. 5B is a perspective view of an upper portion of the control unit ofFIG. 5A;

FIG. 5C is a plan view of an exemplary control panel for the controlunit of FIG. 5A;

FIGS. 5D-5F are perspective views of a lower portion of the control unitof FIG. 5A having exterior panels removed to expose interior components;

FIG. 5G is a perspective view of the control unit lower portion andshowing a heat exchange cassette-receiving subassembly exploded above aninner cavity;

FIG. 6A is a perspective view of the heat exchange cassette-receivingsubassembly seen in FIG. 5G;

FIG. 6B is an exploded view of the heat exchange cassette-receivingsubassembly of FIG. 6A;

FIG. 6C is an exploded view of a heater/cooler unit of the heat exchangecassette-receiving subassembly of FIG. 6A;

FIGS. 7A-7D are various perspective views of a lower guide assembly andpump drive mechanism of the heat exchange cassette-receiving subassemblyof FIG. 6A;

FIG. 8 is a schematic diagram of exemplary components of the presentinvention, illustrating communication and feedback interconnectionstherebetween;

FIG. 9 is a perspective view of a disposable heat exchange cassetteattached to a heat exchange catheter and an external fluid source, andpositioned for insertion into a suitable opening in the reusable controlunit of the present invention;

FIG. 10A is an exploded view of a first disposable heat exchangecassette for use in the present invention;

FIG. 10B is a plan view of one end of the heat exchange cassette of FIG.10A illustrating fluid flow through a bulkhead and attached externalheat exchanger;

FIG. 10C is an exploded perspective view of a reservoir section of thebulkhead of FIG. 10B;

FIG. 10D is a schematic plan view of a fluid pressure damper of thebulkhead of FIG. 10B;

FIGS. 11A and 11B are sectional views take along line 11—11 through theexternal heat exchanger of FIG. 10A, and showing the heat exchanger inits uninflated and inflated states, respectively;

FIGS. 12A-12B are inverted perspective views of an exemplary fluidfitting for use with the external heat exchanger of FIG. 10A;

FIG. 13A is an exploded view of a second disposable heat exchangecassette for use in the present invention;

FIG. 13B is a plan view of one end of the heat exchange cassette of FIG.13A illustrating fluid flow through a bulkhead assembly and attachedexternal heat exchanger;

FIGS. 13C-13D are plan and sectional views, respectively, of thebulkhead assembly of FIG. 13B;

FIG. 13E is an exploded perspective view of a reservoir section of thebulkhead assembly of FIG. 13B;

FIG. 14A is a perspective exploded view of a feedblock section of thebulkhead assembly of FIG. 13B;

FIG. 14B is a simplified plan view of the feedblock section of FIG. 14Aillustrating in hidden lines a fluid pressure regulating mechanismtherein;

FIG. 14C is a slightly magnified view of a portion of the pressureregulating mechanism of FIG. 14B;

FIG. 14D is a cross-sectional view of the automatic priming valve of thefeedblock section of FIG. 14A, with the valve in a “run” orientation;

FIG. 14E is a cross-sectional view of the automatic priming valve of thefeedblock section of FIG. 14A, with the valve in a “prime” orientation;

FIG. 14F is a cross-section taken along the line 14F—14F in FIG. 14C;

FIG. 14G is a cross-section taken along the line 14G—14G in FIG. 14C;

FIG. 15A is a perspective exploded view of a pump section of thebulkhead assembly of FIG. 13B;

FIG. 15B is a plan view of the pump section of FIG. 15A;

FIG. 15C is a sectional view through the pump section taken along line15C—15C of FIG. 15B;

FIG. 15D is a schematic plan view of the geometry of a pump head withinthe pump section of FIG. 15A;

FIGS. 16A-16C are elevational views of alternative embodiments of a pumpvane for use in the pump section of FIG. 15A;

FIGS. 17A-17B are plan and elevational views, respectively, of a pumphead driven gear engaged with a drive mechanism of the re-usable controlunit; and

FIGS. 18A-18C are schematic illustrations of the fluid flow usingdifferent embodiments of the disposable heat exchange cassette ofpresent invention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The present invention is primarily intended to include a catheter placedin the bloodstream of a patient for regulating the patient's bodytemperature, although those of skill in the art will understand thatvarious other applications for the system of the present invention arepossible. Indeed, the present invention may have applications beyondcontrolling the temperature of an internal body fluid, and the claimsshould not be so limited. In a preferred application, one or more of theheat exchange catheters of the present invention are positioned within apatient's vasculature to exchange heat with the blood in order toregulate the overall body temperature, or to regulate the temperature ofa localized region of the patient's body. Heat exchange fluid is thencirculated through the catheter to exchange heat between the blood andthe heat exchange fluid, and a controller manages the functioning of thesystem. The catheters may be, for example, suitable for exchanging heatwith arterial blood flowing toward the brain to cool the brain, and maythus prevent damage to brain tissue that might otherwise result from astroke or other injury, or cooling venous blood flowing toward the heartto cool the myocardium to prevent tissue injury that might otherwiseoccur following an MI or other similar event.

In general, the invention provides a preferred control unit and methodfor controlling the temperature and flow of heat transfer fluid for aheat transfer catheter used for controlling the body temperature of apatient. The control unit initially automatically supplies heat transferfluid to the heat transfer catheter to prime the heat exchange catheterfor use. It also receives input from the user, receives temperatureinformation from sensors that sense patient temperature information, andbased thereon, automatically controls the temperature of the heattransfer fluid. Further, based on feedback from a pump in a cassettecontaining the heat transfer fluid, the control unit supplies heattransfer fluid at a relatively constant pressure. The cassette and thecontroller, working together, have several warning or alarm states thatwarn the user of dangerous situations, for example, by shutting down thepump motor and notifying the user if the fluid level in the cassette isunacceptably low.

Overview of Heat Exchange System

Any suitable heat exchange catheter may be utilized in a heat exchangesystem for regulating the temperature of a patient or a region of thepatient's body and controlled by the control unit as disclosed herein.In addition to the catheters disclosed herein, and by way ofillustration and not of limitation, catheters that may be utilized inthis invention are the catheters disclosed in U.S. Pat. No. 5,486,208 toGinsburg, U.S. Pat. No. 5,837,003 to Ginsburg, WO 00/10494 to Ginsburget al., and U.S. Pat. No. 5,624,392 to Saab, the complete disclosure ofeach of which is hereby incorporated in full herein by reference.

One example of such a heat exchange catheter system 20 is shown in FIG.1, and includes a control unit 22 and a heat exchange catheter 24 formedwith at least one heat transfer section 44. The heat transfer section orsections are located on that portion of the catheter 24, as illustratedby section 26, that is inserted into the patient. This insertion portionis less than the full-length of the catheter and extends from thelocation on the catheter just inside the patient, when the catheter isfully inserted, to the distal end of the catheter. The control unit 22may include a fluid pump 28 for circulating a heat exchange fluid ormedium within the catheter 24, and a heat exchanger component forheating and/or cooling circulating fluids within the heat transfersystem 20. A reservoir or fluid bag 30 may be connected to the controlunit 22 to provide a source of heat transfer fluid such as, saline,blood substitute solution, or other biocompatible fluid. A circulatoryheat exchange flow channel within the catheter may be respectivelyconnected to inlet 32 and outlet 34 conduits of the pump 28 forcirculation of the heat transfer fluid through the balloon to cool theflow of body fluid such as blood within a selected body region. Asimilar arrangement may be implemented for heating of selected bodyregions simultaneously or independently of each other using the coolingcomponent of the system.

The control unit 22 may further receive data from a variety of sensorswhich may be, for example, solid-state thermocouples to provide feedbackfrom the catheter and various sensors to provide patient temperatureinformation representing core temperature or temperature of selectedorgans or portions of the body. For instance, sensors may include atemperature probe 36 for the brain or head region, a rectal temperatureprobe 38, an ear temperature probe 40, an esophageal temperature probe(not shown), a bladder temperature probe (not shown), and the like.

Based upon sensed temperatures and conditions, the control unit 22 maydirect the heating or cooling of the catheter in response. The controlunit 22 may activate a heat exchanger at a first sensed temperature toheat fluid which is then circulated through the balloon, and may alsode-activate the heat exchanger at a second sensed temperature which maybe relatively higher or lower than the first sensed temperature or anyother predetermined temperature. Alternatively, the control unit mayactively cool the heat exchange fluid to cool the balloon. The controlunit 22 may operate multiple heat transfer units to independently heator cool different selected heat transfer sections to attain desired orpreselected temperatures in body regions. Likewise, the controller 22may activate more than one heat exchanger to control temperature atparticular regions of the patient's body. The controller might alsoactivate or de-activate other apparatus, for example external heatingblankets or the like, in response to sensed temperatures.

The regulation exercised over the heat transfer catheters or otherdevices may be a simple on-off control, or may be a significantly moresophisticated control scheme including regulating the degree of heatingor cooling, ramp rates of heating or cooling, proportional control asthe temperature of the heat exchange region or patient approaches atarget temperature, or the like.

The control unit 22 may further include a thermoelectric cooler andheater (and associated flow conduits) that are selectively activated toperform both heating and cooling functions with the same or differentheat transfer mediums within the closed-loop catheter system. Forexample, a first heat transfer section 42 located on the insertionportion 26 of at least one temperature regulating catheter 24 maycirculate a cold solution in the immediate head region, oralternatively, within a carotid artery or other blood vessel leading tothe brain. The head temperature may be locally monitored withtemperature sensors 36 positioned in a relatively proximate exteriorsurface of the patient or within selected body regions. Another heattransfer section 44 of the catheter 24 also located on the insertionportion 26 may circulate a heated solution within a collapsible balloonor otherwise provide heat to other body locations through heat elementsor other mechanisms described in accordance with other aspects of theinvention. While heat exchange catheter 24 may provide regionalhypothermia to the brain region for neuroprotective benefits, otherparts of the body may be kept relatively warm so that adverse sideeffects such as discomfort, shivering, blood coagulopathies, immunedeficiencies, and the like, may be avoided or minimized. Warming of thebody generally below the neck may be further achieved by insulating orwrapping the lower body in a heating pad or blanket 46 while the headregion above the neck is cool. It should be understood of course thatmultiple heat exchange sections of the catheter 24 may be modified toprovide whole body cooling or warming to affect body core temperature.

Exemplary Heat Exchange System

The present invention contemplates the use of a re-usable controller orcontrol console having a heater/cooler device therein and which receivesa disposable heat exchange element coupled via conduits to a distalin-dwelling heat exchange catheter. More specifically, the controllerdesirably includes an outer housing having an opening or slot forreceiving the heat exchange element, the opening and housing ensuringreliable positioning of the heat exchange element in proximity with theheater/cooler device. In this manner, set up of the system isfacilitated because the operator only needs to fully insert and seat theheat exchange element into the controller opening in order to couple thereusable and disposable portions of the system.

In an exemplary embodiment, FIG. 2 illustrates a heat exchange cathetersystem that includes a re-usable control unit 50 and a plurality ofdisposable components including a heat exchange catheter 52, a heatexchange element 54, a saline bag 56, sensors 58 a, 58 b and associatedwires 60 a, 60 b, and a plurality of fluid flow conduits including atwo-way conduit 62 extending distally from the heat exchange element 54.The re-usable control unit 50 includes an outer housing 64 within whichis provided a heater/cooler 66, a pump driver 68, and a controllerprocessor 70. In addition, a manual input unit 72 enables an operator toenter desirable operating parameters of the controller, for example apreselected temperature for the brain. Each of the electronic devicesprovided within the control unit 50 communicate through suitable wiring.

The heat exchange catheter 52 is formed with a catheter conduit 74 and aheat exchanger 76 which may be, for example, a heat exchange balloonoperated using a closed-loop flow of a biocompatible fluid that servesas the heat exchange medium. The catheter 52 may include a working lumen(not shown) for injection of drugs, fluoroscopic dye, or the like, andfor receipt of a guidewire 78 for use in placing the catheter at anappropriate location in the patient's body. A sensor 80 may be providedon the catheter 52 distal to the heat exchanger 76 to monitor thetemperature of the heat exchange balloon, and other sensors (not shown)may be provided as desired to monitor the blood temperature at thedistal tip of the catheter, at the proximal tip of the balloon, or atany other desired location along the catheter.

As seen in FIG. 2, the proximal end of the catheter conduit 74 may beconnected to a multi-arm adapter 82 for providing separate access tovarious channels in the catheter 52. For example, a first arm 84 mayprovide access to the working lumen of the catheter 52 for insertion ofthe guidewire 78 to steer the heat exchange catheter to the desiredlocation. Where the heat exchanger 76 is a heat exchange balloon forclosed-loop flow of a heat exchange medium, the adapter 82 may contain asecond arm 86 connected to an inflow line 88, and a third arm 90connected to an outflow line 92. The inflow line 88 and outflow line 92are therefore placed in flow communication with respective inflow andoutflow channels (not shown) provided in the conduit 74 and heatexchanger 76. In this regard, the inflow and outflow lines 88, 92 maycome together to form the dual channel conduit 62 connected to the heatexchange element 54. Furthermore, an external fluid source such as thesaline bag 56 may be placed in fluid communication with the outflow line92 via a conduit 94 a and a T-junction 94 b. As will be explainedfurther below, the external fluid source is used to prime theclosed-loop heat exchange balloon system.

Alternatively, the external fluid source may be directly connected tothe heat exchange unit 54.

Still with reference to FIG. 2, the heat exchange unit 54 desirablyincludes a heat exchange plate 96 and a pump head 98. The pump head 98pumps heat exchange fluid through a serpentine fluid pathway 100 in theheat exchange plate 96, and through the associated conduits and catheter52. As mentioned, the heat exchange unit 54 is configured to installinto the re-usable control unit 50. In this regard, the heat exchangeunit 54 is desirably plate-shaped and sized to fit through an elongateslot 102 in the control unit housing 64. Once inserted, the pump head 98is placed in proximity to and engaged with the pump driver 68, and theheat exchange plate 96 is placed in proximity to and in thermalcommunication with the heater/cooler 66. A solid-state thermoelectricheater/cooler 66 is particularly advantageous because the same unit iscapable of either generating heat or removing heat by simply changingthe polarity of the current activating the unit. Therefore, theheater/cooler 66 may be conveniently controlled so as to supply orremove heat from the system without the need for two separate units.

The pump driver 68 engages and activates the pump head 98 to cause it tocirculate heat exchange fluid through the heat exchange unit 54 and theserpentine path 100 in the heat exchange plate 96. Therefore, when theheat exchanger unit 54 is properly installed in the control unit 50, theheater/cooler 66 may act to heat or cool the heat exchange fluid as thatfluid is circulated through the serpentine pathway 100 and thereafterthrough the conduits leading to the in-dwelling heat exchanger 76. Whenthe heat exchange fluid is circulated through the heat exchanger 76located in the patient's body, it may act to add or remove heat from thebody. In this way, the heater/cooler 66 regulates the blood temperatureof the patient as desired.

The heater/cooler 66 and a pump driver 68 are responsive to thecontroller processor 70. The processor 70 receives data input throughelectrical connections 104 to numerous sensors, for example bodytemperature sensors 58 a, 58 b positioned to sense the temperature atvarious locations within the patient. For example, the temperature maybe sensed at the patient's ear, brain region, bladder, rectum,esophagus, or other appropriate location as desired by the operator.Also, as mentioned, a sensor 80 may monitor the temperature of the heatexchanger 76, and other sensors along the catheter 52 may provide inputto the controller processor 70, such as via a wire 60 c. Additionally,by means of the manual input unit 72, an operator provides the operatingparameters of the control system such as, for example, a pre-selectedtemperature for the brain and/or the whole body of the patient. Theoperator input parameters are communicated to the controller processor70 by means of appropriate wiring.

The controller processor 70 coordinates the various data received andselectively actuates the several operational subsystems to achieve andmaintain desired results; i.e., proper regulation of the patient's bodytemperature. For example, the processor 70 may actuate the heater/cooler66 to increase the amount heat it is removing if the actual temperatureis above the specified temperature, or it may decrease the amount ofheat being removed if the temperature is below the specifiedtemperature. Alternatively, the processor 70 may stop the pumping of theheat exchange fluid when the sensed body or regional temperature reachesthe desired temperature.

Referring still to FIG. 2, the disposable heat exchange unit 54 of theinvention is shown as being attached to a heat exchange catheter 52,external fluid source 56 is positioned in cooperation with a suitablereusable control unit 50. Prior to commencing treatment, theheat-exchange unit 54 is inserted into the reusable control unit 50, theexternal fluid source 56 is attached to the fill port and the pump 98 isautomatically or passively primed and the disposable system filled,after which the catheter is ready for insertion in-the vasculature ofthe patient, for example in the inferior vena cava or the carotidartery. Chilled or warmed biocompatible fluid such as saline, is pumpedinto the closed circuit catheter, which exchanges heat directly with thepatient's blood. The control unit serves to automatically-control thepatient's temperature. Once treatment with the catheter is complete, thecatheter is removed from the patient and the cassette is removed fromthe reusable control unit. Both the catheter and cassette are thendiscarded. The reusable control unit, however, which never comes intodirect contact with.the heat exchange fluid, is ready for immediate usefor treatment on other patients, along with a new cassette and catheterand fresh external fluid source.

Exemplary Method of Temperature Control

The flowchart seen in FIGS. 3A and 3B illustrates an exemplary sequenceof steps that the controller processor 70 coordinates during temperatureregulation of a patient. First, in step 110, a target temperature forthe target tissue (which may be the entire body) is selected, generallyby user input. The target temperature may be different than the bodytemperature, or may be the same if maintenance of normal patienttemperature is the goal. Steps 112 a and 112 b involve determination ofan upper variance set point and a lower variance set point,respectively. This is generally a pre-set buffer range above and belowthe target temperature that is built or programmed into the controllerprocessor. These variance set points straddle the target temperature andcreate a buffer range of temperature within which the controlleroperates.

More specifically, the sensed temperature for the target tissue isobtained in step 114 prior to or after step 116 in which a heatexchanger capable of either heating or cooling body fluid is placed inproximity with body fluid that subsequently flows to the target tissue.Based on user input, or on a comparison between the target temperatureand the sensed tissue temperature, a determination is made in step 118as to whether the heat exchanger will be operating a cooling mode, aheat mode, or will remain off. That is, if the target temperature equalsthe tissue temperature then there will be no need to initially heat orcool the body fluid.

The determination step 118 leads to three different modes of operationof the system, depending on whether the system will be COOLING, HEATING,or OFF. These modes of operation correspond to steps 120 a, 120 b, and120 c, which appear on both the FIGS. 3A and 3B.

If the system is in the COOLING mode, the flowchart logic leads to step120 a which compares the sensed.tissue temperature with the pre-selectedtarget temperature. If the tissue temperature is greater than the targettemperature, the system continues cooling as indicated in step 122, andthe processor 70 returns to decision step 118. On the other hand, if thesensed tissue temperature is equal to or less than the targettemperature, the heat exchanger is converted to the OFF mode asindicated in step 124 and the processor 70 returns to decision step 118.

If the system is in the HEATING mode, the flowchart logic leads to step120 b which also compares the sensed tissue temperature with thepre-selected target temperature. If the tissue temperature is less thanthe target temperature, the system continues heating as indicated instep 126, and the processor 70 returns to decision step 118. On theother hand, if the tissue temperature is equal to or greater than thetarget temperature, the heat exchanger is converted to the OFF mode asindicated in step 128, and the processor 70 returns to decision step118.

If the system is in the OFF mode, the flowchart logic leads to step 120c which compares the sensed tissue temperature with the upper variancetemperature set point. Then, if the sensed tissue temperature is equalto or greater than the upper variance set point, the system is convertedto the COOLING mode as indicated in step 130, and the processor 70returns to decision step 118. If the tissue temperature is less than theupper variance set point, the processor continues to step 132 in theflowchart logic, and determines if the tissue temperature is equal to orless than the lower variance set point, whereby the system is convertedto the HEATING mode and processor 70 returns to decision step 118.Finally, if the tissue temperature is between the upper and lowervariance set points, the system does nothing as indicated in step 134,and the processor 70 returns to decision step 118.

FIG. 4 is a graphical illustration plotting the fluctuating sensedtissue temperature over a period of time relative to the targettemperature and variance set points. In the example, the targettemperature is set at 31 degrees Celsius, with the upper and lowervariance set points ½ degrees on either side. Initially, the sensedtissue temperature is greater than the target temperature, such as ifthe heat exchange catheter is placed in contact with blood at 37 degreesCelsius. The system is first placed in the COOLING mode so that thesensed tissue temperature is reduced until it equals the targettemperature at 136, corresponding to steps 120 a and 124 in FIG. 3A. Instep 124, the heat exchanger is converted to the OFF mode, which resultsin the sensed tissue temperature climbing until it reaches the uppervariance set point at 138, corresponding to step 130 in FIG. 3B, atwhich time the system begins cooling again. This cycle is repeated inthe region indicated at A.

Eventually, the patient may be unable to maintain even the targettemperature as shown by the temperature profile in the region indicatedat B. For example, after the sensed tissue temperature reaches thetarget temperature at 140, and the heat exchanger is turned OFF, thesensed target temperature may continue to drift lower until it reachesthe lower variance set point at 142. The controller logic senses this instep 132 of FIG. 3B, and converts the system to the HEATING mode.Subsequently, the sensed tissue temperature climbs to the targettemperature at 144, and the system is again turned OFF, corresponding tosteps 120 b and 128 in FIG. 3B. Alternatively, depending on the patientand the situation, it may be that after the sensed tissue temperaturereaches the target temperature and the heat exchanger is turned OFF, thepatient's temperature may begin to increase until it rises to the uppervariance set point temperature, at which point, as described in box 130the heat exchanger begins to COOL. As can be appreciated, the sensedtissue temperature continues to fluctuate between the upper and lowervariance set points in this manner.

The control scheme as applied to the system of the present invention hasthe advantage of allowing the operator to essentially input a desiredtemperature after which time the system will automatically regulate thetissue temperature until it reaches the target temperature, and willmaintain the tissue temperature at that target temperature. The bufferrange created by the upper and lower variance set points prevents thecontroller from turning the heater/cooler on and off or activating andde-activating the pump driver in rapid succession, actions that would bepotentially damaging to these electric devices.

Exemplary Heat Exchange Control Unit

FIGS. 5A-5F are various views of an exemplary heat exchange control unit150 of the present invention that is particularly suited for rapidtemperature regulation of a patient.

As seen in the Figures, the control unit 150 comprises avertically-oriented outer housing having a lower portion 152 and upperportion 154 separated at a generally horizontal dividing line 156located close to the top of the unit. The control unit 150 is mounted onwheels 158 for ease of portability, with the wheels preferably being ofthe swivel type having foot-actuated locks. For ease of servicing, theupper and lower portions may be joined together with hinges 155 at theback so that the top portion may be lifted up and rotated back to exposethe interior of the unit. In an exemplary embodiment, the control unit150 has a height that enables an operator to easily access an uppercontrol panel 160 without the need for significant bending. For example,the control unit 150 may have a total height of between approximately2-3 feet, and preferably about 32 inches. The substantially horizontalcross-section of a majority of the control unit 150 may have widths ofbetween one and two feet, although the lower portion 152 preferablywidens at its lower end with the wheels 158 mounted on the lower cornersto provide greater stability.

FIG. 5A illustrates the assembled control unit 150, while FIGS. 5B-5Gshow various exploded views and subassemblies of the control unit. FIG.5A illustrates the front and right sides of the unit 150 wherein thecontrol panel 160 is visible on an angled upper panel 162 of the upperportion 154 front side. The angled upper panel 162 also defines a fluidcontainer receiving cavity 164 adjacent the control panel 160. Further,a plurality of handles 166 may be provided to help maneuver the controlunit 150.

A heat exchange cassette-receiving opening 168 is also provided on afront panel 169 of the control unit 150, just below the horizontaldividing line 156. As will be explained below, the opening 168 is sizedand shaped to receive a heat exchange cassette of the present invention,analogous to the heat exchange cassette-receiving opening 102 shown inFIG. 2. Likewise, the control unit 150 provides all of the features thatwere described above for the control unit 50 of FIG. 2, including aheater/cooler, a pump driver, a controller processor/microprocessor, anda manual input unit, namely the control panel 160.

Because of the relatively high capacity for heating and cooling, thelower portion 152 of the control unit housing includes a plurality ofvents 170 to facilitate convective heat exchange between the interior ofthe housing and the surrounding environment. The control unit housingmay be manufactured of a number of suitably strong andcorrosion-resistant materials, including stainless-steel, aluminum, ormolded plastic. Desirably, the components of the control unit 150 areadapted to run on conventional power from a catheterization lab poweroutlet, for example.

The present invention also contemplates the use of two different controlunits in sequence, depending on need. For example, the control unit 150of FIGS. 5A-5F having a relatively large heat transfer capacity andlarge housing can be used initially to rapidly alter the patient's bodytemperature. Subsequently, a smaller unit having an internal batterypower source can be substituted for convenience and economy. Both thelarge and small control units desirably define the same sized andconfigured cavity for receiving a cassette of the present invention. Inthis manner, the cassette may be de-coupled from one unit, the patienttransported with the cassette in place to another location without thefirst unit, and the cassette coupled to another unit for a subsequentoperation/therapy. The present invention also encompasses a situationwherein the cassette is de-coupled from a first unit and then coupled toa second unit of the same size. This simply obviates the need totransport control units with the patient.

Exemplary Control Panel

FIGS. 5B and 5C illustrate in greater detail the upper portion 154 ofthe control unit 150, and in particular the control panel 160. FIG. 5Bshows a facade 172 exploded from the control panel 160, with the facadeshown in FIG. 5C having indicia printed thereon corresponding to variousdisplays and buttons. (The reader will notice that the control panel 160in FIG. 5C is an alternative embodiment from one shown in otherdrawings, and includes several added features and with several buttonsand/or displays being slightly relocated). The following is adescription of the physical characteristics of the control panel 160,with a description of an exemplary method of using the control panel tofollow later in the description.

The exemplary control panel 160 of FIG. 5C provides a number of visualdisplays, including, from top to bottom along the centerline, a patienttemperature display 174, a target temperature display 176, acooling/warming rate display 178, and a system feedback/status display180. Other desirable information may be displayed, either with anadditional display, or alternating with information displayed on one ofthe screens shown here, or by user initiated request from one of thescreens shown here. For example, by way of illustration but notlimitation, if the ramp rate for heating or cooling the patient is setby the user, or is calculated by a control microprocessor, or theprojected time to target temperature is calculated, those values may beshown. The larger displays for alphanumeric characters are preferablyliquid crystal displays (LCD), while several light emitting diode (LED)status indicators are also provided. Several graphic icons arepositioned adjacent the left of the upper three LCD displays 174,176,and 178, to indicate their respective display functions. Specifically, apatient temperature icon 182 a, a target temperature LED 182 b, and acooling/warming rate LED 182 c are provided. Just below thecooling/warming rate LED 182 c, an operational mode LED 182 d andassociated vertical series of three mode indicators 184 are provided.Only one of the indicators 184 lights up at any one time, depending onwhether the system is in the COOLING, WARMING, or MAINTAINING mode. Inlieu of the mode indicators 184, the display 180 may carry the messageCOOLING PATIENT, WARMING PATIENT, or MAINTAINING so that the operatorcan easily identify the mode of functioning of the controller. Therealso may be only one patient temperature icon 182 which has a line oflights that streams upward if the unit is warming, downward if the unitis cooling, and blinks stationary if the unit is maintaining. Finally, apower on/off indicator LED is provided in the lower left corner of thecontrol panel 160.

The control panel 160 also exhibits a number of input buttons including,in descending order on the right side of the control panel, aCelsius/Fahrenheit display toggle 190, a pair of target temperatureadjustment buttons 192, a pair of cooling/warming rate adjustmentbuttons 194, a multi-function/enter button 196, and a mute audible alarmbutton 198. The mute audible alarm button 198 is nested within an LEDalarm indicator 200. Finally, in the lower central portion of thecontrol panel 160, a stop system operation button 202 permits instantshutdown of the system.

Control Unit Housing

As seen in FIGS. 5D-5G, the control unit housing is defined by a numberof panels, some of which can be removed to view and access the interiorcontents of the control unit 150. For example, in FIGS. 5D and 5F, thefront panel 169 (FIG. 5A) has been removed to expose an internal cavity210 a majority of which is filled by a subhousing 212 enclosing arelatively large blower fan (not shown). As will be explained below, theblower fan within the subhousing 212 interacts with a thermoelectriccooler/heater, and is separated therewith by a circular upper opening214 that receives a gasket 216 to seal about a circular skirt 244(described below with respect to FIG. 6A). An air filter 218 covers anopening 220 in the bottom of the subhousing 212 within the control unitsuch that room air pulled into the subhousing 212 through the opening214 is filtered. Finally, a drain cup 222 may be provided in the bottomof the control unit 150. In FIG. 5E a rear panel has been removed toexpose a rear cavity 224 from which a number of electric connectors 226are accessible.

FIG. 5G is a frontal perspective view of the lower portion 152 of thecontrol unit 150 showing a heat exchange cassette-receiving subassembly240 exploded upward from the inner cavity 210. The subassembly 240 isshown isolated in FIGS. 6A and 6B, and defines a heat exchangecassette-receiving cavity 242 (FIGS. 6B) on a front side thereof thatregisters with the similarly-sized opening 168 in the front panel 169when the subassembly is within the cavity 210. By this arrangement, aheat exchange unit of the present invention, such as a heat exchangeunit 54 of FIG. 2, or a heat exchange cassette as described below, canbe inserted through the front panel opening 168 and “plugged-in” to thecavity 242 within the subassembly 240.

As seen in both FIGS. 5G and 6A, the tubular skirt 244 depends from thesubassembly 240 and includes a lower flange 246 having a series ofthrough holes therein to enable attachment around the circular opening214 in the blower subhousing 212 (FIG. 5D) with the gasket 216 heldtherebetween. The skirt 244 thus provides a direct and contained pathwayfor the air blown upward by the blower for cooling the subassembly 240.Alternatively, the pathway for the air may be reversed, with the blowerpulling air downward through the subhousing 212. The subassembly 240further includes a plurality of mounting brackets 248 that securelyattach to a similar number of support brackets provided in the cavity210 of the control unit 150.

Heat Exchange Cassette-Receiving Subassembly

FIGS. 6A-6C further illustrate the various components of the heatexchange cassette-receiving subassembly 240 in several views and withseveral portions removed or exploded. With reference first to FIG. 6B,the subassembly 240 comprises, from top to bottom, an upper pressureplate 260, a pair of elongated side spacers 262, an upper guide assembly264, a lower guide assembly 266, a pump drive mechanism 268 attached toand depending downward from the lower guide assembly, a rear waterchannel assembly 270, a heater/cooler subsystem 272, and an air cooler274 dispose directly below the heater/cooler subsystem. In addition, afluid level measurement sensor module 276 is shown exploded in FIG. 6B,and is adapted to be mounted to the underside of the lower guideassembly 266.

The air cooler 274 comprises a hollow box-like structure having solidfront and rear walls, a circular opening (not shown) in the bottom wallto communicate with the interior of the tubular skirt 244, and a pair ofside walls with vents 278 that register with the vents 170 in thesurrounding control unit housing. In addition, the air cooler 274 isexposed to the underside of the heater/cooler subsystem 272. This isaccomplished by fastening a portion of the heater/cooler subsystem 272over the open-topped box of the air cooler 274, as will be described ingreater detail below with respect to FIG. 6C. In this manner, air blownthrough the tubular skirt 244 (either upward or downward) flows past theunderside of the heater/cooler subsystem 272. If the air is blownupward, it is redirected sideways through the vents 278 and 170 to theexternal environment. If the air is blown downward, it is pulled inthrough the vents 278 and 170 and is redirected downward through thefirst filter in the circular upper opening 214, and out through thesecond air filter 218 covering the square opening 220 to the externalenvironment. The air cooler 274 therefore acts as a highly efficientconvective heat sink for the heater/cooler subsystem 272. Of course,other types of heat sinks and other patterns of convective air coolingmay be used, and the present invention should not be considered limitedto the air blower 274 shown.

FIG. 6C shows the heater/cooler subsystem 272 exploded with an upperplate 280 separated from a lower plate 282 and between which a pluralityof thermoelectric (TE) modules 284 are sandwiched in thermal contactwith both. As mentioned previously, the lower plate 282 fastens over theopen top of the box-shaped air cooler 274. The TE modules 284 arepreferably discrete modules distributed over the surface of the lowerplate 282. In exemplary embodiment illustrated, there are twelve squareTE modules 284 distributed in rows and columns across substantially theentire area of the lower plate 282. The TE modules 284 preferablyfunction on the well known Peltier principal, wherein the same TEmodules may either heat or cool depending on the direction of DC currentthrough the units. Therefore, merely by changing the polarity of thecurrent flowing through the TE module the heater/cooler subsystem can beinstantly changed from a heater to a cooler or visa versa. The amount ofheat or cold generated can also be adjusted by controlling the amount ofcurrent flowing through the TE modules. Thus a very high level ofcontrol may be exercised by control of only one variable, the DC currentsupplied to the TE modules.

The upper plate 280 provides a conductive heat transfer interfacebetween TE modules 284 and the heat exchange cassette inserted withinthe cavity 242, and tends to distribute the discrete temperaturedifferentials provided by the TE modules 284 over its surface. Thishelps to prevent localized heating or cooling of the heat exchangecassette, which may provoke an erroneous temperature measurement.Further, the upper plate 280 is manufactured of a suitably rigid metalhaving good thermal conductivity, such as anodized aluminum or othersuitable material. The rigidity of both the upper plate 280 and theupper pressure plate 260 are sufficient to resists bending from fluidpressurization of the heat exchange cassette positioned in the internalcavity 242.

With reference again to FIGS. 6A and 6B, connection of the variouscomponents of the subassembly 240 creates the aforementioned internalcavity 242 into which a heat exchange cassette of the present inventioncan be inserted. In the preferred embodiment, a cassette is provided asdescribed in greater detail below comprising a relatively thick bulkheadportion and a relatively thin external heat exchanger, with the externalheat exchanger sized to fit between the upper pressure plate 260 and theupper plate 280 of the heater/cooler assembly 272. In this regard, thelower guide assembly 266 includes a pair of upstanding side walls 290 a,290 b each having guide slot 292 a, 292 b facing inward toward theother. The guide slots 292 a, 292 b are sized to receive the side edgesof the desirably plate-like external heat exchanger and reliablydirected it into the narrow gap defined between the upper pressure plate260 and the upper plate 280. Although not shown, a micro-switch isdesirably provided in the slot 292 of one of the upstanding side walls290 to indicate when-the heat exchange cassette has been fully insertedinto the internal cavity 242, and is engaged therein for properoperation of the system. Also not shown but well known in the relevantart, registration means such as pressure pins or balls and matingdetents may be provided in the control unit and cassette respectively toaid in the correct relative positioning between the cassette and thecontrol unit.

FIGS. 6B an 6C illustrate a thermistor 294 positioned in asimilarly-shaped receptacle 296 in one edge of the upper plate 280 ofthe heater/cooler subsystem 272. The thermistor 294 may be of a standardtype well known in the art and generally available, and is secured inthe receptacle 296 with a fastener, such as the screw shown exploded inthe figures. The thermistor 294 senses the temperature of the upperplate 280 and is connected (not shown) to transmit the information tothe control processor of the control unit 150. The temperature of theupper plate 280 provides a surrogate temperature of the heat exchangefluid within the heat exchange cassette positioned in the internalcavity 242. That is, the temperature of the working fluid at the heatexchanger is measured indirectly by sensing the temperature of the upperplate 280. This indirect method has been shown to work adequately, butof course a more direct measurement of the fluid temperature is withinthe scope of the invention.

The heat exchange cassette-receiving subassembly 240 further includes asystem for driving a pump provided in the heat exchange cassette. Morespecifically, as mentioned above with respect to FIG. 6B, and as shownin more detail in FIGS. 7A-7D, the pump drive mechanism 268 is attachedto the underside of the lower guide assembly 266 for powering a pump inthe heat exchange cassette. As shown from below in FIG. 7C, the pumpdrive mechanism 268 preferably includes an electric motor attached tothe underside of the lower guide assembly 266 and having an output shaft(not shown) engaged with a drive belt 300 that, in turn, rotates a pumpdrive shaft 302 via a pulley 304, the drive shaft being journaled torotate within a vertical through bore in the lower guide assembly 266.Other alternative methods of transferring rotational motion from thepump drive motor are clearly anticipated by this disclosure and mayinclude a series of gears between the electric motor and the outputshaft, a direct drive mechanism whereby the electric motor directlyengages the pump in the cassette, or other similar configurations.

With respect to FIGS. 7A and 7B, the upper end of the drive shaft 302 islocated within an irregular channel 306 formed in the top side of thelower guide assembly 266. The upper end of the drive shaft 302 presentsa drive gear 308. Although not shown, an exemplary heat exchangecassette of the present invention includes a downward projection thatfits within the channel 306 and includes a pump head gear 774 in FIG.15A that engages drive gear 308. A pair of idler hubs 310 a, 310 b mayalso be provided to engage the pump shaft idler wheels and position thepump head gear in engagement with the drive gear 308. A series ofrelated pins and bearings are shown in the drawings, but will not befurther explained with the understanding that a skilled artisan wouldunderstand the various functional and design alternatives.

FIGS. 7A-7D also illustrate a cavity 312 formed in the underside of thelower guide assembly 266. A series of through holes 314 extend betweenthe cavity 312 and the top side of the lower guide assembly 266. As seenin FIG. 7B, a transparent window 316 fits into a correspondingly-sizedrecess 318 and covers the holes 314. A fluid level measurement sensormodule 276 seen in FIGS. 6A and 6B fastens within the cavity 312 andincludes optical transmitters/sensors that are placed in registry withthe openings 314 and interact with the heat exchange cassette to providean indication of fluid level within the unit, as will be furtherexplained below.

Electronic Control Circuit of the Present Invention

As an alternative to the control system described in conjunction withFIGS. 3A-3B and the graph of FIG. 4, the controller may employ acascading PID control scheme. In such a scheme, a control system isprovided that may be divided into two sections: (a) a Bulk PID controlsection which takes input from the user (in the embodiment shown, RAMPRATE and TARGET TEMPERATURE) and input from the sensors on the patientrepresenting patient temperature, and calculates an intermediate setpoint temperature (SPI) and an output signal to the Working Fluid PIDcontrol; and (b) the Working Fluid PID control, that receives input fromthe Bulk PID control section and from a sensor representing thetemperature of the working fluid, and generates a signal that controlsthe temperature of the TE cooler by varying the power input to the TEcooler. The working fluid circulates in heat transfer proximity to theTE cooler, so the Working Fluid PID essentially controls the temperatureof the working fluid. In this way, the control scheme is able toautomatically achieve a specified target temperature at a specified RAMPRATE based on input from sensors placed on the patient and the logicbuilt into the controller. Additionally, this scheme allows the unit toautomatically alter the patient temperature very gradually the last fewtenths of a degree to achieve the target temperature very gently andavoid overshoot or dramatic and potentially damaging swings in theelectronic power to the TE cooler. Once the target temperature isachieved, the system continues to operate automatically to add or removeheat at precisely the rate necessary to maintain the patient at thetarget temperature.

Specifically, this is achieved as illustrated in FIG. 8. FIG. 8illustrates an exemplary control schematic of components of the presentinvention specifically adapted for use in control unit 150 of FIG. 5A,but applicable to any control unit described herein. Some of theseelements correspond to elements identified previously, and thus, whereappropriate, reference numbers will be repeated for clarity. In general,the control circuit includes a control board having a number of logicalcomponents indicated within the dashed line 322, a user input 324, adisplay output 326, a plurality of sensors 328, a number of elements ofelectronic hardware indicated within the box 330, and a safety system332. The user inputs 324 and display outputs 326 were described abovewith respect to the control panel 160 of FIG. 5C. The two user inputs324 applicable to the control circuit in this embodiment are the targettemperature adjustment buttons 192 and cooling/warming rate adjustmentbuttons 194. The display outputs 326 applicable to the control circuitare the patient temperature display 174 and the alarm display 200, butmay include a number of other displays for various feedback to the user.A plurality of sensors 328 may be provided, including at least a sensor327 that senses the patient's actual body temperature and generates asignal represented by line 326, and a sensor 329 that directly orindirectly senses the temperature of the working fluid and generates arepresentative signal 331. As stated previously, the working fluid maybe, for example, saline that is heated or cooled by passing in heatexchange proximity with a TE cooler 348 and then is circulated within aheat exchange catheter.

After the system is primed, a set point temperature (SP1) is determinedwith a set point calculator 334 using the target temperature and thedesire ramp rate as inputs. This set point temperature represents aninterim target temperature that the system will achieve at any giventime, for example 0.1° C. each 6 minutes, if the ramp rate is 1° C. perhour, starting with the initial patient temperature. This set pointtemperature is transmitted to a Bulk PID control section 336 of thecontrol board. The Bulk PID control 336 also receives input from thebody temperature sensor 327.

Based on the differential between the SP1 and actual body temperature,if any, the Bulk PID control 336 raises or lowers the temperaturespecified for the heat exchange fluid that will be circulated throughthe exchange catheter so as to induce a change to the patienttemperature at the specified ramp rate. That is, a value for the desiredworking fluid temperature, or a second set point temperature (SP2), istransmitted to a Working Fluid PID control unit 338 as illustrated at337. The Working Fluid PID control unit 338 also receives input from thetemperature sensor 329 for the working fluid as illustrated at 333. TheWorking Fluid PID control unit 338 compares the sensed working fluidtemperature with the desired working fluid temperature transmitted fromthe Bulk PID control to determine a differential, if any. Based on thisdifferential, the Working Fluid PID control 338 transmits a digitalsignal as illustrated at 340 to an “H-Bridge” polarity switching unit342, which directs power of an appropriate magnitude and polarity to theTE cooler 348 to cause the TE cooler to be heated or cooled toward thedesired temperature.

This, in turn, heats or cools the working fluid as the system operatesto circulate the working fluid in heat exchange proximity to the TEcooler.

The polarity switching unit 342 receives power from a source 344 andtransforms that power to the appropriate magnitude and polarityrequested by the Working Fluid PID control unit. Between the powersource and the polarity switching unit is a safety relay 346 actuated bythe safety system 332 that will, in the absence of a safety issue,transmit the power from the power source 344 to the polarity switchingunit 342. If the safety system 332 is aware of a safety issue, forexample if a low fluid level is sensed, it may direct the safety relay346 to open and prevent power from the power supply 344 from beingdirected to the TE cooler 348. In the absence of any safety issue,however, the polarity switching unit 342 transmits the power to theheater/cooler unit 348 in accordance to the request from the WorkingFluid PID control unit. Various subsystems of the present inventionprovide input to the safety system 332, and will be described below whenintroduced.

The control circuit includes logic that permits rapid heat exchange whenthe target temperature and the sensed body temperature are relativelyfar apart, and which slows down the rate of heat exchange as the sensedbody temperature nears the target temperature. As the sensed patienttemperature and the SP1 become very close, the Bulk PID will dictateonly a very small change in the working fluid temperature, and thus therate of change will become smaller and smaller as the SP1 becomes veryclose to the sensed patient temperature until the rate of change isessentially non-existent. In this way, the patient temperature verygently is heated or cooled the last few tenths of a degree, avoidingovershoot or dramatic swings from heating to cooling when the bodytemperature is at the target temperature. As the input TARGETTEMPERATURE is reached, the SP1 and the TARGET TEMPERATURE areessentially the same, and the system operates to set the power to the TEcooler at a level that maintains the necessary working fluid temperatureto hold the patient temperature at the TARGET TEMPERATURE. In this way,the system will work to maintain a target temperature with the workingfluid maintained at just the right temperature to add or remove heat atthe precise rate necessary to maintain that target temperature asessentially a steady state.

The Working Fluid PID control 338 samples its respective inputs at arate of 10 times a second and updates the output to the polarityswitching unit 342 at a rate of once every second, and thus the trendsof changing patient temperature are constantly monitored and adjusted.The Bulk PID control 336 samples its inputs at the same rate, and thus anew target temperature or a new ramp rate can be specified by the userwith nearly instantaneous system response.

A First Exemplary Heat Exchange Cassette

Suitable heat exchange cassettes for use in the invention are describedin U.S. patent application Ser. No. 60/185,561 incorporated in fullherein by reference. Such catheters are generally described below.

FIG. 9 schematically illustrates an exemplary heat exchange cassette 400of the present invention shown adjacent to a receiving opening 402 in acontrol unit 404. The control unit 404 may be configured like element 50described above with reference to FIG. 2, or like element 150 withreference to FIGS. 5-8. Consequently, the control unit 404 includes aheater/cooler mechanism (not shown in FIG. 9), a pump drive mechanism406 (schematically shown), a controller processor, and a manual inputdevice (also not shown in FIG. 9). The pump drive mechanism 406 includesa drive gear 408 and a pair of idler wheels 410, similar to theembodiment shown in FIGS. 7A-7D.

FIG. 9 further schematically illustrates exemplary placement of anoptical beam source 412 and optical beam sensor 414 used to determine afluid level within the heat exchange cassette 400, as will be explainedfurther below. Furthermore, exemplary placement of a valve actuationsystem 416 including, at least, a linear actuator 418 and push rod 420is shown. Finally, it will be appreciated by one skilled in the art thatthe various advantageous features described above with reference toFIGS. 2 and 5-8 may be ascribed to the control unit 404 of FIG. 9.

FIG. 9 illustrates certain aspects of the overall heat exchange cathetersystem of the present invention, as described above with respect to FIG.2, including a heat exchanger 422 on the distal end of an in-dwellingcatheter 424 through which a heat exchange fluid may be circulated viaan inflow line 426 and outflow line 428. The fluid inflow and outflowlines 426, 428 are typically of a flexible compressible material such aspolyvinylchloride or other suitable flexible compressible tubingmaterial, and are fluidly connected to a bulkhead 430 of the heatexchange cassette 400. A fluid supply bag 432 supplies heat exchangefluid for priming the system via a supply line 434 which can be closedthrough the use of a stop cock or pinch clamp 436. Bag size is notgenerally critical but has a typical capacity of about 250 ml. Thedisposable heat exchange cassette 400 can be packaged with or separatelyfrom the heat exchange catheter 424.

The heat exchange cassette 400 comprises the aforementioned bulkhead 430to which an external heat exchanger 440 is coupled via a cover plate442. As mentioned above, the external heat exchanger 440 issubstantially flat and thin so as to fit within a narrow slot or gapprovided within the control unit 404 and be sandwiched between aheater/cooler plate and a pressure plate. The bulkhead 430 is somewhatthicker and is provided with a handle 444 to facilitate insertion andremoval from the control unit 404. Additionally, the bulkhead 430 dockswithin an outer portion of the opening 402 such that the pump drivemechanism 406 engages a pump head therein. Exemplary details of the pumphead will be provided below. (It should be noted that the Figures depicttwo different embodiments of the bulkhead. The bulkhead shown in FIG. 9is described in greater detail with respect to FIGS. 10B, 13A-13E and14A-14E.)

It should also be reiterated that the control unit 404 comprises are-usable component of the entire system, while the heat exchanger 440,catheter 424, and fluid supply 432 comprise disposable components.Indeed, in a preferred embodiment, all the components except for thecontrol unit 404 are packaged together in a sterile pre-assembled unit.This arrangement enables the medical staff to set up the entire systemby simply opening up the sterile package, “plugging-in” the heatexchange cassette 400 into the control unit 404, and introducing thecatheter 424 into the appropriate location in the patient. After theprocedure is over, everything but the control unit 404 is disposed of.With reference now to FIGS. 10A and 10C-10D, an exemplary heat exchangecassette 400 a of the present invention will be described. As describedabove, the exchange unit 400 a includes a bulkhead 430 a, an externalheat exchanger 440 a, and a cover plate 442 a. The bulkhead 430 aincludes a reservoir section 450 and a pump section 452 shown explodedin FIG. 10A, and coupled together for fluid communication in FIG. 10B.

The cutaway plan view of FIG. 10B shows a number of flow arrows thatindicate the flow path of heat exchange fluid through the bulkhead 430 aand external heat exchanger 440 a. Beginning from an external fluidsource 454, such as the fluid bag 432 shown in FIG. 9, an inlet line 456primes the reservoir section 450, and fluid is then pumped to the rightin the drawing through an L-shaped outlet channel 458 (FIG. 10C) andinto an inlet 459 of the pump section 452. The outlet of the pumpsection 452 leads to the conduit 460 that supplies the in-dwellingcatheter. After circulating through the indwelling heat exchangecatheter, the working fluid flows back into a flow-through channel 497in the pump section 452 and through an outlet 462 on the upper sidethereof leading to the external heat exchanger 440 a and a flow channeldefined therewithin. After passing through the heat exchanger 440 a,fluid flows back into an inlet 464 of the reservoir section 450 of thebulkhead 430 a.

With reference still to FIGS. 10A and 10C-10D, but with particularreference to the perspective view of FIG. 10C, the reservoir section 450comprises a lower container 470 that includes, as a top wall, an uppercover plate 472 closely received in a stepped rim of the container andis fastened thereto by a biocompatible.adhesive. The container 470defines a fluid cavity 474 therewithin which receives fluid from twosources: a supply inlet 476 to which the external fluid source conduit456 attaches, and the inlet 464 connected to the interior of theexternal heat exchanger 440 a. The L-shaped channel 458 provides a fluidoutlet located at the end of the reservoir section 450 fluidly connectedto the pump inlet 459. Located at the same end of the reservoir as theL-shaped channel is a damping chamber 478 that is not open to thereservoir. A compressible material.480, such as a block of foam, isassembled into the damping chamber 478. The function and advantage ofsuch a damping chamber 478 will be described further below.

The cover plate 472 seals around the edge of the container 470 to createthe fluid cavity 474, but is provided with one or more vent holes 484fitted with hydrophobic gas-permeable vents permitting the release ofair from within the cavity. The vent holes 484 permit air to bedisplaced from within the container 470 when fluid is introduced thereinduring a system priming operation, without permitting escape of anyfluid therefrom. The pore size on the vent holes 484 is small enough toprevent the entrance of any contaminants such as microbes, thusmaintaining the sterility of the fluid that is being circulated throughthe catheter in the patient's body. First and second prisms 486 a, 486 bare also located within the container 470 as part of a fluid leveldetection system, to be described further below. The location of theprisms in this embodiment are adjacent the wall of the damping chamber478, but on the embodiment shown in FIG. 9 are at the other end of thereservoir, and are attached as shown in FIG. 13E at 590 a, 590 b. As oneof skill in the art will readily recognize, the location of the prisms,and the function whether vertical or horizontal is a matter of designchoice, and requires concomitant changes in the location of the opticalbeam sensors 412, 414 in the control unit.

As seen in FIG. 10B, the pump section 452 includes a rotating-type pumphead 490 defined within a quasi-cardioid shaped cavity 492 The pump head490 includes a rotor 494 and a movable vane 496, and rotates on a shaft(not numbered) that is driven by an external source, such as the pumpdrive mechanism 406 seen in FIG. 9. The pump head 490 is desirably ableto pump fluid through the system at pressure in excess of 35 psi and,more preferably, is able to rapidly achieve and maintain a predeterminedpressure, for example 40 psi. Specific details of the pump head 490 willbe provided below with respect to FIGS. 15-16, it being understood thatthe rotating-type pump can be a vane pump as shown, an impeller pump, ora gear pump. Furthermore, with some modification, the present system canutilize other types of fluid pumps, such as diaphragm pumps orperistaltic pumps.

The pump section 452 also has the aforementioned flow-through channel497 having a fluid coupling inlet means 498 that leads from the catheterdirectly to the outlet 462 leading to the external heat exchanger 440 a.As seen in FIGS. 10B and 10D, a diverging pump outlet channel 499 is influid communication with a fluid coupling outlet to the catheter 460,and also to the pressure dampening chamber 478. The pressure dampingchamber may be filled with, for example, a block of compressiblematerial 480 in fluid communication with the fluid flowing to thecatheter. If fluid from the pump flowing to the catheter is experiencingpressure fluctuations, the fluid is exposed to the compressible material480 within the dampening chamber 478, and as fluid column contacts thecompressible material 480, the material compresses slightly or expandsslightly, and in doing so acts to absorb pressure fluctuations in thefluid that may result from the action of the pump. The compressiblematerial thus has the effect of dampening pressure pulses in the fluidflow to the catheter.

Suitable examples of the compressible material include a block of foam,encapsulated foam such as polyethylene foam encased in a polyethylenefilm, foam enclosed within a sealed plastic pouch, foam coated with orimpregnated with plastic or silicone, gas encapsulated within a flexiblepouch such as a polyethylene balloon, and so forth.

Exemplary External Heat Exchanger

The external heat exchanger shown as 440 in FIG. 9 and 440a in FIG. 10Acan be any combination of one or more structural and compliant memberssuch that the overall configuration of the external heat exchanger isadapted to mate with the opening provided in the control unit 404 a. Ina preferred embodiment, as seen in the cross sections of FIGS. 11 A and11 B, the structural member comprises a planar back plate 500 and thecompliant member comprises a layer 502 of flexible, thermally conductivematerial. The compliant layer 502 is sealed to the back plate 500 in apattern which forms a serpentine flow channel 504 therebetween, as seenin FIG. 10A. The flow channel 504 includes a fluid inlet orifice 506provided with a flow fitting 508, and a fluid outlet orifice 510provided with an identical flow fitting 512. The flow fittings 508 and512 are seen in perspective in FIGS. 12A and 12B.

The back plate 500 is typically stiff and made of a high densitypolyethylene and is generally about 0.762 mm (0.030 inches) thick. Thethinner compliant layer is shown in this embodiment as being sealed in aserpentine pattern to the back plate by fusing, such as by heat sealingor other suitable technique to permanently adhere the two layerstogether. The pattern of heat sealing creates a serpentine pathwaycomposed of sealed portions 514 separating the continuous serpentineflow channel 504 or, alternatively, a plurality of flow channels.

The winding flow channels 504 form a pathway which causes the heatexchange fluid to flow back and forth adjacent to and in heat transferrelationship with the heater/cooler device within the control unit 404a, and ensures that the fluid circulates proximate to the heatheater/cooler device for a sufficient amount of time to allow foradequate heating or cooling of the fluid. The present invention also mayutilize sealed portions that are not continuous, as long as the sealedportions are configured so as to create channels that permit fluid flowthrough the external heat exchanger 440 a. In addition, the externalheat exchanger can be configured to have a V-shaped leading edge 516that acts as a guide to facilitate placement into the control unit 404.

The thinner compliant layer 502 is generally about 0.102-0.203 mm(0.004-0.008 inches), and is typically a low density polyethylenematerial that is slightly elastomeric or compliant so that whenpressurized heat exchange fluid flows into the legs of the serpentinechannels 504, they bow out slightly as may be seen by comparing FIG. 11A(uninflated) and FIG. 11B (inflated). Since the back plate 500 andthinner compliant layer 502 are both polyethylene, they weld togethereffectively by means of heat fusion or ultrasonic welding. However, thebulkhead 430 a is not the same material, and therefore the external heatexchanger is generally sealed to the bulkhead by other means, such as bya mechanical pressure seal.

As seen in FIG. 10A, the external heat exchanger 440 a is provided withan extended attachment 520 that is sealed to the bulkhead 330. Theextended attachment. 520 has three sections distributed across thebulkhead 330; a first flap section 522 a, a cutaway section 522 b, and asecond flap section 522 c. One or more vent holes 524 are cut into thefirst flap section 142 to allow air to vent from the correspondingnumber of hydrophobic gas permeable vents 484 in the reservoir coverplate 472, as was described above. While a plurality of vent holes 524is shown in the embodiment of FIG. 10A, any suitable shape or number ofholes will suffice, for example a single vent hole.is shown in theembodiment of FIG. 13A, infra.

As mentioned, each of the orifices 506, 510 opening to the serpentinechannels 504 is provided with a fitting 508, 512 that allows fluid toflow into the space between the thin compliant layer 502 and the backplate 500. When heat exchange fluid is pumped into the inlet orifice 506through the first fitting 508, it winds its way along the serpentinepath to the outlet orifice 510 and then enters the bulkhead through thesecond fitting 512. The entire external heat exchanger 440 a is placedin thermal contact with a heater/cooler within the control unit 404,such as the heat exchange surface of a thermoelectric cooler or a numberof TE cooler modules in contact with a thermal plate (as shown in FIG.6C). The thinner compliant layer 502 is positioned against the heatexchange surface so that the temperature of heat exchange fluid may becontrolled by controlling the temperature of the surface and pumpingfluid through the external heat exchanger.

The fittings 508, 512 are secured within the inlet and outlet orifices506, 510 by virtue of their particular construction, as illustrated inFIGS. 12A and 12B. Each fitting 506, 510 has a central channel 530, abase plate 532, a plurality of spacer protrusions 534 on the lowersurface of the base plate, and a nose 536 projecting in the oppositedirection from the base plate 532. The embodiment of FIG. 12Billustrates four such protrusions but the invention contemplates havingfewer or more than four protrusions. When the fitting 506 is placed inthe external heat exchanger 440 a, the nose 536 projects through theinlet orifice 506, and the base plate 532 is tightly positioned betweenthe compliant layer 502 and the back plate 500. The spacer protrusions534 space the base plate 532 away from the back plate 500 of theexternal heat exchanger. At the outlet orifice 510, fluid containedwithin channels 504 passes between the protrusions, through channel 530,and then into bulkhead 430 a. Similarly, fluid returning from the heatexchange catheter enters the heat exchange channels 504 through thecentral channel 530 in fitting 506, and passes between the protrusions534. Two O-rings, such as flexible rubber.washers, can be positionedaround the periphery of the nose 536 of each fitting 506, 510 betweenthe compliant layer 502 and the bulkhead 430 a. The noses 536 of eachfitting 506, 510 are sized to be inserted into the: associated outlet462 and inlet 464 of the bulkhead 430 a.

A Second Exemplary Heat Exchange Cassette

FIGS. 13A-13E illustrate a second exemplary heat exchange cassette 400 bthat is in many ways similar to the first-described heat exchangecassette 400 a, but has a bulkhead assembly that includes a feedblocksection and pressure valve as described below. As in the earlierembodiment, the exchanger 400 b includes a bulkhead assembly 430 bcoupled to an external heat exchanger 440 b through the use of coverplate 442 b.

The bulkhead assembly 430 b includes a reservoir section 550 a pumpsection 552 and a feedblock section 554 disposed therebetween. Thesethree sections can be independent and discrete units that are coupledtogether, as seen in FIG. 13A, or may be defined within a single unit.The bulkhead section(s) can be machined, molded, or cast, and aretypically made of the durable, lightweight material such as plastic orPLEXIGLAS.

With reference to the perspective views of FIGS. 13A and 13E, the hollowreservoir section 550 has an elongated rectilinear shape with a pair ofcollars on one longitudinal end facing the feedblock section 554:namely, a fluid outlet collar 560 defining a reservoir outlet channel561 and a pressure regulator collar 562. These two collars securelyengage two collars of slightly smaller size on the juxtaposed end of thefeedblock section 554; specifically, as seen in FIG. 14A, a fluid inletcollar (not shown) and a pressure sensing chamber collar 564. Thefeedblock section 554 is also a hollow, generally rectilinear housingand includes, on the side facing the pump section 552, an inlet collar566 leading to an inlet conduit 568, a first outlet collar 570 openingfrom a first outlet conduit 572, and a second outlet collar 574 openingfrom a second outlet conduit 576. A series of O-rings 578 are sized tofit around each of these collars 566, 570, 574 and ensure fluid tightseals between the collars and associated openings formed in thejuxtaposed side of the pump section 552.

a. Exemplary Reservoir Section

With reference still to FIGS. 13A-13E, but with particular reference tothe perspective view of FIG. 13E the reservoir section 550 comprises alower container 580 that includes, as a top wall, an upper cover plate582 closely received in a stepped rim of the container which may befurther affixed with adhesive or heat welding or other acceptablefastening method. The container 580 defines a fluid cavity 584therewithin which receives fluid from a single source: an inlet 586connected to the interior of the external heat exchanger 440 b. Thecover plate 582 seals the fluid cavity 584 around the edge of thecontainer 580, but is provided with one or more vent holes 588 fittedwith hydrophobic gas-permeable vents permitting the release of air fromwithin the cavity during a priming operation.

First and second prisms 590 a, 590 b are also located within thecontainer 580 adjacent a transparent bulkhead material or window 591 aspart of a fluid level detection system. As seen in FIG. 13D, the lowercontainer 580 can be configured so as to have an indented or sloped area592 in the base. The sloped or indented area defines a fluid channel orsump from the interior fluid cavity 584 of the reservoir adjacent theprisms 590 a, 590 b to the fluid outlet 561. In this way the fluidopening leading to the reservoir outlet channel 561 is at approximatelythe same elevation as the prisms 590 a, 590 b which will thereforeassure fluid to the pump even if the level of fluid at the prisms isquite low. As will be discussed below, the prisms are safety systems fordetecting low fluid level, a potentially dangerous condition, and theindented area 592 adds extra insurance that a low fluid level will bedetected before an absence of fluid to the pump becomes a problem.

As seen in FIG. 13E, a pressure regulator shaft 598 mounts in the fluidreservoir cavity 584 through a mounting flange 600 extending into thecavity from one of the side walls of the container 580. In oneembodiment, the pressure regulator shaft 598 includes threads which matewith internal threads provided in a through hole 602 in the flange 600.A reference spring 604 is biased between the shaft 598 and a diaphragm606. The diaphragm 606 may be a membrane, for example, acloth-reinforced silicone membrane. Because of the presence of thehydrophobic gas permeable vents 588, the pressure on the reservoir sideof the diaphragm 606 is essentially atmospheric pressure plus thepressure applied by reference spring 604. The pressure of referencespring 604 may be adjusted by advancing or retracting the shaft 598within the threaded hole 602, which in turn adjusts the amount of springforce applied against the diaphragm. A pressure plate 608 is interposedbetween the diaphragm 606 and the reference spring 604 to more evenlydistribute the pressure of the spring to the reservoir side ofdiaphragm. Further specifics of this exemplary pressure regulatingmechanism of the present invention will be described below.

b. Cover Plate

As with the earlier described heat exchange cassette 400 a, the externalheat exchanger 440 b of FIG. 13A includes an extended attachment flange610 that is secured to the upper side of the bulkhead assembly 430 b bythe cover plate 442 b. Preferably, a mechanical seal is formed betweenthe attachment flange 610 and the bulkhead assembly 430 b by virtue of anumber of fasteners (not shown) extending between the cover plate 442 band the bulkhead assembly. The cover plate 442 b includes a handle 612for ease of manipulation of the heat exchange cassette 400 b.

The cover plate 442 b further includes a plurality of apertures andgrooves that interact with the bulkhead assembly 430 b, and also withthe re-usable control unit of the present invention, such as theexemplary control unit 404 of FIG. 9. For example, an elongated aperture614 registers with a similarly shaped aperture 616 in the attachmentflange 610, both apertures permitting passage of air from the reservoirsection vents 588.

The cover plate 442 b further has a priming valve aperture 618 thatpermits access to a flexible diaphragm of the feedblock section 554, asdescribed below. Furthermore, the cover plate 442 b is configured tohave one or more indicators to alert the user that the heat exchangecassette is in the correct position for operation. For example, thecover plate may have a slot that operates to depress a switch on thecontrol unit to indicate proper placement, such as a switch in thereceiving opening 402 of the exemplary control unit 404 of FIG. 9.Similarly, the cover plate 442 b may have slots 620, leading todepressions 622 that received biased detents such a spring loadedbearings on the control unit. When the heat exchange cassette 400 b isbeing positioned within the control unit, the detents will be guidedalong the slots 620, and once the unit is fully inserted the detentswill cam into the depressions 622 with an audible click to inform theuser that placement is complete. As one of skill in the art willunderstand, a more secure positive locking arrangement may be provided,although as will be described below, pressurization of the external heatexchanger 440 b serves to hold the heat exchange cassette 400 b tightlywithin the re-usable control unit.

c. Fluid Pathway Through Second Heat Exchange Cassette During AutomaticPrime

Prior to a detailed description of the sections of the bulkhead assembly430 b, fluid flow through the heat exchange cassette 400 b will begenerally explained. When the external fluid source has been attached tothe feedblock 554, the system is initially filled with fluid and purgedof air before insertion into a patient. This process is called priming.The priming is done automatically by the cassette in conjunction withthe control unit depicted in FIG. 9. The control unit initiallyactivates a priming push rod 420 that depresses a flexible membrane 672on the cover plate above the valve actuating rod 680.

This positions the valve in the feedblock to the “prime” position (FIG.14E) so that fluid from the fluid source enters a fluid fill reservoir682 a, and is directed toward the pump through pump feed line 640. Thefeed line from the reservoir is closed and fluid enters from the fluidbag, to the pump, thence through the pressure regulating chamber, thecatheter, back into the heat exchange unit, through the serpentine path,and into the reservoir. As the reservoir fills, the air that isdisplaced is expelled through the hydrophilic valves. Once the reservoiris full, the fluid level detectors signal the control unit that thereservoir is full, and the prime valve is deactivated, so that pus rod420 withdraws, flexible membrane 672 relaxes, and the valve actuatingrod, 680, which is biased by spring 678 to the upward position, returnsto the “run” position. In this position, the priming valve is positionedin the run position (FIG. 14D) and fluid is pumped in a closed circuitfrom the reservoir, through the pump, through the pressure regulatingchamber, through the catheter, back into the heat exchange unit acrossthe TE cooler through the serpentine path, and into the reservoir.

To better explain this priming sequence, a number of fluid flow arrowsare indicated in FIGS. 13B, 14D and 14E. An external fluid source 630attaches to a fill port 632 leading to a fill channel 634 incommunication with a central chamber 636 of the feedblock section 554(also see FIG. 14A). The fluid outlet collar 560 of the reservoirsection 550 directs fluid to the central chamber 636 via an internalchannel 638 in the feedblock section. A further internal channel 640(FIG. 14A) of the feedblock section 554 provides an outlet from thecentral chamber 636 leading to the first outlet conduit 572 definedwithin the first outlet collar 570, and, ultimately, to the pump section552.

Initially the system is primed as described in the next section. Thisfills the reservoir, the catheter, and the external heat exchanger withfluid and expels the air in the system. The system is then in the RUNcondition, whereby fluid is pumped in a closed circuit in approximatelythe following pathway, seen best with reference to FIGS. 13B and 13C.The pump section 552 includes a rotary-type pump head 642 that propelsfluid through an outlet channel 644 past a pressure regulating chamber646 in the feedblock section 554 via the inlet conduit 568 within theinlet collar 566. The pressure regulating chamber 646 has an outletchannel 648 and outlet port 650 to which a catheter inflow line 652(FIG. 13B) couples. The fluid is pumped through the heat exchangecatheter from the outlet channel. After passing through the heatexchange catheter, fluid returns through an outflow line 654 thatcouples to an inlet port 656 (FIGS. 13C and 14A). The return heatexchange fluid then passes through a relay channel 658 and passes out ofthe feedblock section 554 through the second outlet conduit 576 withinthe second outlet collar 574. Fluid then passes through a flow throughchannel 660 within the pump section 552 leading to a bulkhead outlet662, as also seen in FIG. 13A.

The bulkhead outlet 662 leads to one or more internal flow channelsprovided within the external heat exchanger 440 b. As with theearlier-described embodiment, the heat exchanger 440 b may be anycombination of one or more structural and compliant members such thatthe overall configuration is adapted to mate with the opening providedin the control unit 404 a. For instance, the heat exchanger 440 b may beconstructed as seen and described with respect to the cross sections ofFIGS. 11A and 11B. Namely, the heat exchanger 440 b may include a rigidback plate 500 and a layer 502 of flexible, thermally conductivematerial sealed to the back plate 500 in a pattern which forms aserpentine flow channel 504 therebetween. The aforementioned flowfittings 508 and 512 seen in FIGS. 12A and 12B are also desirably usedto facilitate inflow and outflow from the serpentine flow channel 504.

After passing through the flow channel 504 within the heat exchanger 440b, fluid enters the reservoir cavity 584 through the bulkhead inletorifice 586. And finally, from the reservoir section 550, fluid passesthrough the outlet collar 560 back into the central chamber 636 of thefeedblock section 554.

Alternatively, the system of the present invention can be passivelyprimed, and the fluid level maintained without resort to a switchingvalve as described above. That is, a fluid supply bag may be attached soas to drain by gravity to prime the system. At the same time there is nobackflow valve and the bag accepts excess fluid if, for example, thefluid expands when heated. If the heat exchange balloon leaks and thecircuit starts to empty, the bag will continue to fill the system untilThe bag is empty, then the reservoir level will begin to drop. When itdrops to a predetermined low level, a fluid level detector will sensethe low level, sound an alarm and shut the flow off. A small fluid bag(e.g., 250 cc's maximum) is desirable so that if there is a leak aminimum amount of heat exchange fluid such as saline will be pumped intothe patient. Such a small volume of saline is not considered a medicalrisk to the patient.

d. Exemplary Feedblock Section

FIGS. 14A-14G illustrate the component parts of the exemplary feedblocksection 554 that provides one embodiment of a priming valve and a fluidregulator for the heat exchange catheter system of the presentinvention. As mentioned, the central chamber 636 has a first inlet influid communication with an external fluid source 630, a second inlet influid communication with the reservoir section 550, and an outlet influid communication with the pump section 552. A priming valve 670mounted within the central chamber 636 regulates flow into the centralchamber from either of the first and second inlets, depending on thefluid level within the reservoir section 550. The priming valve 670includes, from top to bottom in FIG. 14A, a flexible membrane 672, anannular guide disk 674 having a central orifice 675, a valve member 676,a valve spring 678, and a valve stem 680. As seen in FIGS. 14D and 14E,these components are arranged within the central chamber 636, whichactually comprises a series of three gradually smaller steppedsubchambers 682 a, 682 b, 682 c.

The solid flexible membrane 672 covers the central chamber 636, and moreparticularly, seats within a counter bore 684 and is fastened therein,such as with adhesive. A push rod, such as the push rod 420 in thereceiving opening 402 of the control unit 404 seen in FIG. 9, ispositioned to pass through the priming valve aperture 618 in the coverplate 442 b and displace the flexible membrane 672 downward which, inturn, displaces the valve member 676 downward, as seen in FIG. 14E. Thepush rod 420 is desirably not contained in the heat exchange cassette400 b, and may be manually triggered or automatically controlled such asby the valve actuation system 416 of FIG. 9. The push rod 420 may act,for example, by means of the linear actuator 418 displacing the push roddownward upon a signal from the processor of the control unit 404,triggered by full insertion of the heat exchange cassette 400 b into thereceiving opening 402 of the control unit 404.

Once the valve member 676 is displaced downward, the aforementioned fillchannel 634 (FIG. 13B) brings fluid from the external fluid source 630to the upper, largest subchamber 682 a. The guide disk 674 seats againsta shoulder 686 at the bottom of the upper subchamber 682 a that definesa transition between the upper subchamber and the middle subchamber 682b. The middle subchamber 682 b opens to the outlet channel 640, and alsosteps to the smaller lower subchamber 682 c. The lower subchamber 682 c,in turn, receives fluid from the reservoir section 550 via the inletchannel 638. The rigid valve stem 680 is fixedly position within acavity in the floor of the lower subchamber 682 c, and extends upwardinto the upper subchamber 682 a. The valve member 676 includes aninternal cavity 688 that receives the upper end of the valve stem 680 soas to permit relative linear movement therebetween. The valve spring 678surrounds the valve stem 680 and is placed into compression between thevalve member 676 and floor of the lower subchamber 682 c.

The valve member 676 has a lower annular flange 690 extending outwardfrom concave shoulders that receive and seat a pair of O-rings 692. Thevalve member 676 translates linearly along the valve stem 680 such thatthe O-rings 692 alternately contact the underside of the guide disk 674(FIG. 14D), and the floor of the middle subchamber 682 b (FIG. 14E). Thespring 678 normally biases the valve member 676 upward along the valvestem 680 such that the upper O-ring 692 seals against the underside ofthe guide disk 674. In this default position, seen in FIG. 14D, fluidflows from the reservoir section through the inlet channel 638, lowersubchamber 682 c, middle subchamber 682 b, and through the outletchannel 642 toward the pump head 552. Alternatively, during priming ofthe system, the push rod 420 is displaced downward, as seen in FIG. 14E,displacing the valve member 676 downward such that the lower O-ring 692contacts and seals against the floor of the middle subchamber 682 b. Inthis mode of operation, fluid flows from the fill channel 634 into theupper subchamber 682 a, through an annular space between the valvemember and the central orifice 675 of the guide disk 674, through themiddle subchamber 682 b, and through the outlet channel 642 toward thepump head 552.

e. Exemplary Pressure Regulator

A pressure regulator valve to regulate the pump output pressure isdesirable. Any pressure regulator that down-regulates pressure may beused in the pressure line between a pump outlet 744 and the outlet port650 to down-regulate the pressure from the pump to the desired supplypressure for the heat exchange catheter. A pressure regulator inaccordance with the present invention may also function to dampen anypressure variations, such as vibrations in the fluid line generated bythe pump.

One such pressure regulator is illustrated in the feedblock section 554of the heat exchange cassette 400 b of FIG. 14A. The exemplary pressureregulation system is seen in FIGS. 14B-14C and 14F-14G, and comprises aspring-biased diaphragm that flexes to relieve pressure above athreshold value and ensure that heat transfer fluid is provided to thecatheter at a relatively constant pressure. For clarity of illustration,FIG. 14B is simplified by removing the priming valve describedpreviously with respect to FIGS. 13B and 13C from the drawing, althoughin the actual embodiment, the feedblock section contains both elements.

With reference to FIG. 14B, the pump outlet 744 fluidly connects to theinlet of the pressure regulating chamber 646. Fluid pressure at the pumpoutlet may vary somewhat depending on wear and fluid temperature, and isgenerally higher than the desired supply pressure for the heat exchangecatheter. For example, a catheter supply pressure of about 40 psi may bedesired, while the pump outlet pressure may be, for example, 45-54 psi.Therefore, the fluid pressure must be down-regulated before beingdirected to the catheter. As described in detail below, the presentinvention provides an apparatus and method of down regulating thepressure by directing the fluid flow through a narrow throttle thatautomatically adjusts to create a pressure drop of precisely the correctamount.

As mentioned previously with respect to FIG. 13E, a portion of thepressure regulator resides within the reservoir chamber 684 and includesthe pressure regulator shaft 598 mounted for linear adjustment withinthe flange 600, and a reference spring 604 biased between the shaft andthe diaphragm 606. As seen in FIGS. 14A and 14B, a push rod 700 attachesto the diaphragm 606 on the feedblock side, and extends through athrottle chamber 702 into the pressure regulating chamber 646. Thepressure regulating chamber 646 is in fluid communication with a fluidchannel 704 that is in turn in communication with the pump outlet 744. Apressure regulating disk 706 is fixed within the fluid channel 704 and,as best seen in FIGS. 14C and 14F, and has a generally annular outerdisk 708, an annular axially-extending lip 709 sized about half thediameter of the disk, and a plurality of radial fingers 710 extendinginward from the disk to define a cloverleaf opening 712 therein. Thefingers 710 extend radially inward into proximity with the rod 700 so asto act as a centering guide for the rod.

The rod 700 contacts or is attached to the center of a throttle plate714, having a generally square configuration with rounded corners, asseen in FIGS. 14A and 14G. Arcuate gaps 716 are thus defined between thethrottle plate 714 and the cylindrical fluid channel 704. The diaphragm606, rod 700, and throttle plate 714 are free to axially slide to anextent within the surrounding channels formed in the feedblock section554. The throttle plate 714, if in contact with the pressure regulatingdisk, would form a seal against the generally annular lip 709, althoughin actual function, the throttle plate does not come to rest against theannular lip. Instead it is the passage of the fluid through the smallgap existing between the throttle plate, around the annular lip 709, andinto the cloverleaf opening 712 that creates the pressure drop loweringthe fluid pressure from the pressure at the pump outlet to the desiredpressure in the chamber 646.

The throttle plate 714 attaches to a cup-shaped extension 718 thatreceives a relatively weak throttle spring. 720. The throttle spring 720is received on its other end by a hollow spring cap 722 affixed withinthe fluid channel 704. The spring cap 722 includes an opening along itsaxis so that fluid may flow from the pump outlet 744 toward the pressureregulating chamber 646. The diaphragm 606 is biased to the right (towardthe regulating chamber 646) in FIG. 14B by a preset amount equal to thepressure within the reservoir 584 (essentially room pressure because thereservoir is open through the aforementioned hydrophobic valves) plusthe adjustable pressure of the reference spring 604. Through attachmentof the rod 700 to the diaphragm 606, the throttle plate 714 is alsobiased away from the pressure regulating disk 706. On the other side,the weak throttle spring 720 biases the throttle plate 714 slightlytoward the pressure regulating disk, thus keeping the throttle platesnug and oriented.

Fluid from the pump outlet 744 flows through flow channel 704 past thespring cap 722 and through the arcuate gaps 716 around the throttleplate 714. Fluid then flows through the cloverleaf opening 712 in thepressure regulating disk 706 and into the pressure regulating chamber646, from where it flows through the outflow port 650 leading to theheat exchange catheter. As best seen by the arrows in FIG. 14C, fluidflowing through the small arcuate gaps 716 formed around the throttleplate 714 experiences a pressure drop because of the narrow size of thegaps, and from the tortuous path as it flows around the annularaxially-extending lip 709 and through the cloverleaf opening 712. Themagnitude of the pressure drop depends on the spacing between thethrottle plate 714 and pressure regulating disk 706, and increasessignificantly when the spacing decreases because of the nearly rightangle turn of the fluid from the gaps 716 inward around the lip 709.

The action of the flexing of the preset diaphragm and the axial movementof the throttle plate act to automatically adjust the pressure drop tothe desired level so that the pressure in the pressure regulated chamberis constant at the preset pressure. If the pressure from the pumpoutlet, 704 increases, the diaphragm 606.will flex toward the reservoir,and the attached throttle plate 714 will be forced toward the pressureregulating disk. This will narrow the flow openings between the throttleplate 714 and the fixed pressure regulating disk 706, thus increasingthe pressure drop across the components.

Conversely, if the pump outlet pressure decreases, the diaphragm 606will flex outward, moving the push rod away from the reservoir thuscausing the throttle plate 714 to move away from the pressure regulatingdisk 706. This increases the size of the flow openings, thus decreasingthe pressure drop across the components. In this way, the pressureregulating system automatically response to variations in pressure atthe pump outlet 704 to increase or decrease the pressure drop, andmaintain the pressure supplied to the heat exchange catheter at a presetamount, for example 40 psi.

f. Indirect Method of Fluid Pressure Control Using Motor Current

As mentioned above, controlling the pressure and/or flow rate of theheat exchange medium through the heat exchange catheter may beaccomplished by regulating the speed of the pump based on the backpressure of the fluid being pumped. Alternatively, conventional flowmeters may be provided within the fluid conduits. However, each of theseconventional systems presents an additional cost, and may be subject tofailure or error. In addition, such monitoring elements desirably wouldbe designed not to contact fluid directly so as to avoid potentiallycontaminating the fluid. Non-contact flow and pressure sensors typicallyinvolve infrared or ultrasonic devices, which, along with the associatedhardware to interpret the measurements, can be expensive and subject tofailure in use. Consequently, it may be desirable to eliminate thepressure regulator valve, pressure regulator chamber and sensing chamberfrom the cassette design. In that instance, another means of insuringconstant pressure and providing for smooth fluid flow can beincorporated into the cassette design.

Although the present invention encompasses conventional means forcontrolling the flow rate or pressure of the heat exchange medium, apreferred means is to control the current flow through the pump drivemotor. The torque developed by an electric motor is directlyproportional to the current supplied to that electric motor. Where, asin the pump described below, friction within the pump is negligible sothat the torque generated by friction does not vary significantly withpump speed, the fluid pressure developed by a rotating pump vane such asthat described below is directly proportional to torque supplied by theelectric motor operating the pump. (Another way of describing thepressure developed by the pump is back pressure developed by thesystem.) Therefore by controlling the current supplied to the electricmotor at a constant amount regardless of the speed (rpm) developed bythe motor, the pressure output of the pump would be relatively constant.This pressure regulation to a constant current is achieved with a simpleamplification feedback which is well known to those in the art and willnot be described in greater detail here.

Suffice it to say, with reference to the embodiment of FIGS. 5-8, thepump drive mechanism 268 typically comprises an electric motor and apower supply that provides the necessary current to run the motor.Constant current can be attained by directing the voltage from the powersupply to an amplifier which adjusts and controls the fluctuatingvoltage input to provide a constant current output to the motor. With aconstant current supplied to the electric motor that runs the pump, themotor provides for constant torque to the pump head in the disposableheat exchange unit/cassette, which ultimately provides for constantpressure supplied to the fluid to the catheter.

Therefore, in one embodiment of the disposable cassette of theinvention, the cassette comprises an external heat exchanger having aninlet and an outlet, a first fluid supply line in fluid communicationwith the heat exchanger inlet, a disposable pump head having a pumpinlet in fluid communication with the heat exchanger outlet and having apump outlet, a second fluid supply line in fluid communication with thepump outlet for receiving fluid pumped out of the pump outlet, and anoptional pressure regulator in fluid communication with the pump outletfor regulating the pressure of fluid pumped from the pump head. The pumphead is actuated by an electric motor that is controlled by an amplifiercontroller, where the amplifier controller supplies a constant currentto the pump head thereby causing the pump head to supply a relativelyconstant pressure to the fluid in the second fluid supply line.

Exemplary Pump

The pump section 552 is readily adapted for use with the reservoirsection 550 and feedblock section 554 of the heat exchange cassette ofFIG. 13A or the reservoir section 450 of the heat exchanger and 400 a ofFIG. 10A, and is configured to allow for pumping of heat exchange fluidat a constant pressure. In this embodiment of the invention, the pumpingmechanism creates rapid flow in a heat exchange fluid supply system forsupplying a heat exchange fluid to an intravascular heat exchangecatheter, and comprises a cavity having a quasi-cardioid shape, an inletto the cavity, an outlet from the cavity, a pump head comprising a rotorhaving a central groove, and a vane slidably mounted in the groove andimpinging on the edge of the cavity.

An exemplary vane-type pump section 552 is illustrated in FIGS. 15A-15C,where the pump section 550 contains a cavity 720 of quasi-cardioid shapeand the pump head 642. The pump head 642 has a rotor 722 which iscircular and rotates within the cavity 720, and has a central groove 724disposed diametrically thereacross. A vane 726 is slidably mounted inthe groove and impinges on the edge of the cavity 720. As the rotor 722rotates around its center, the vane 726 moves freely, sliding back andforth within the groove 724, with the ends 728 a, 728 b of the vanebeing continuously in contact with the wall of the cavity 720.

With reference to FIGS. 15A and 15C, the rotor 722 is mounted to rotatewith a shaft 730 by means of a pin 732. The shaft 730 rotates within aseal 734 and a bearing 736 separated by an optional spacer 738, providedin a manner known to those of skill in the art of rotating shaftsmounted in a fluid-tight arrangement.

With reference to FIG. 15B, a fluid inlet channel 742 leads from thefeedblock section 554 and opens into the cavity 720 just beyond the edgeof the rotor 722. The aforementioned fluid outlet channel 744 opens intothe cavity 720 on the opposite side of the rotor 722 and leads back tothe feedblock section 554. As the rotor 722 rotates, the vane 726 is inrelatively fluid tight, continuous contact with the cavity wall 740.Fluid enters into the cavity 720 from the inlet channel 742 and iscontained in the cavity between the cavity wall 740, the rotor wall 124and the vane 726. As the rotor 722 rotates the vane 726 also moves. Thiscauses the fluid path to increase in area as it is filled with heatexchange fluid from the inlet channel 742, and then decrease in area asthe vane pushes the heat exchange fluid through outlet channel 744. Theouter wall 746 of the rotor 722 is in relatively fluid tight contactwith the wall 740 of the cavity along arc 748 and therefore fluid cannottravel directly from the inlet channel 742 to the outlet channel 744 ofthe pump. As the rotor rotates, fluid is pumped from the inlet channel742 around the quasi-cardioid shaped cavity and pushed by the vane outthe outlet channel 744. The configuration of the fluid path can belikened to a “crescent” shape, as can be seen in FIG. 15B.

The pump is designed to rotate within the range of 200-1000 rpm and tofunction for up to 72 hours. More specifically, the pump is designed tooperate for significant periods of time, for example in excess of 72hours, at fairly high rotational speeds, for example approximately 800rpm, and to operate on pump fluids at temperatures that vary betweenapproximately 0° C. and 45° C. The choice of materials should beselected to accommodate these needs. For example, the rotor 722 of thepump head is made of a rigid and durable material with adequatelubricity to sustain a long period of close contact with the cavity wall740 (FIG. 15B) while rotating without undue wear. The rotor 722 may bemade of, for example, polyvinylidene fluoride, and the vane 726 may bemade of a material such as high density polyethylene.

It is desirable that the heat exchange catheter is supplied with fluidat a relatively constant pressure at the inlet to the catheter, forexample about 40-46 psi, but wear and temperature variations may affectthe output pressure of the pump. In the embodiment which includes thepressure regulator, the pump is designed to have an output pressureslightly higher than the optimal pressure for the heat exchangecatheter, for example 42-48 psi, and the pressure is regulated don tothe desirable pressure of 40-46 psi. If the output pressure of the pumpvaries, a pressure regulator can be incorporated into the disposableheat exchange cassette to ensure that the heat exchange catheter isprovided heat transfer fluid at a relatively constant pressure. Thepressure regulator can be, for example, a pressure regulator valve asdescribed with reference to FIG. 14B, a pressure damper as seen in FIG.10D, or a constant current regulation of the pump motor.

The rounded ends 728 a, 728 b on the vane 726 provide the additionaladvantage that the point of contact between the vane edges and thecavity wall 740 changes constantly through the rotation of the rotor 722and thus avoids a single wear point on the ends of the vane. This allowsthe vane 726 to rub against the wall 740 of the cavity for as long as 72hours and yet retain a relatively fluid tight contact therebetween. In apreferred embodiment, the vane is designed to fit in the cavity 720 atroom temperature with a slight clearance, for example 0.127 mm (0.005inches). This clearance is one means of accommodating the transient andsteady state thermal changes that occur during operation and allows forexpansion of the vane due to an increase in temperature duringoperation. In this manner, at the temperatures that are encounteredduring normal operation, the vane ends 728 a, 728 b will maintainadequate contact with the wall 740 of the cavity 720 for pumping.

There are numerous other vane designs that also accommodate thermalchanges so that the vane remains in continuous contact with the wall ofthe cavity and is able to move smoothly within the cavity. FIGS. 16A-16Care side views of examples of such designs. In FIG. 16A, a vane 750 isconfigured with cut-out sections 752 a, 752 b, which allow for expansionor contraction of the vane during operation. In FIG. 16B, a vane 754defines a center section 756 made of a compressible material toaccommodate expansion or contraction of the end portions 758 a, 758 bduring operation. In FIG. 16C, a vane 760 includes a center spring 762to bias the end portions 764 a, 764 b outward during operation tocontact the wall of the cavity regardless of the temperature of thevane.

One significant aspect of the invention relates to the geometry of thequasi-cardioid shaped cavity 720, as seen in FIG. 15D. Recalling FIG.15B, the cavity wall 740 includes an inlet 742 and an outlet 744thereto, and is part of the pumping mechanism of the disposable heatexchange cassette 400 b. The pump head 642 of the pumping mechanismcomprises the rotor 722 having a diameter “D” and the aforementioneddiametral groove 724 (FIG. 15A), and the vane 726 having a length “L”and slidably mounted in the groove so as to impinge on the edge of thecavity 740.

As shown in FIG. 15D, the circumference of the cavity 740 can be dividedinto four arcs 770 a, 770 b, 770 c, 770 d, where the radius “R” of eacharc has its center at the center of the rotor 722 and is measured to thecavity wall 740. For orientation purpose, the arcs 770 a, 770 b, 770 c,770 d are defined with reference to the center of the rotor 722, with abase line of 0° identified with the point midway between the inlet andthe outlet of the cavity, i.e., the line projected from the center ofthe rotor 722 and the point on the cavity wall that is midway betweenthe inlet channel 742 and the outlet channel 744 (see FIG. 15B). 0-360°angles are measured, in a clockwise fashion from the base line.

Accordingly, the four arcs are defined as follows: (a) a first arc 770 afrom 330° to 30° and having a radius R₁, (b) a second arc 770 b from150° to 210° and having a radius R₂, (b) a third arc 770 c from 30° to150° and having a radius R₃, and (d) a fourth arc 770 d from 210° to330° and having a radius R₄. The four radii are defined as follows:

R ₁ =D/2

R ₂ =L−(D/2)

R ₃=(D/2)+{[(L−D)/2]·[cos(1.50+135)]}

R ₄=(D/2)+{[(L−D)/2]·[cos(1.50−315)]}

Therefore, arc 770 a is circular and thus has a constant radius R₁; arc770 b is not circular since its radius R₃ changes as the angle ofrotation increases from 30° to 150°; arc 770 c is also circular and thusalso has a constant radius R₂; and arc 770 d is not circular since itsradius R₄ changes as the angle of rotation decreases from 210° to 330°.These calculations are somewhat approximate because the vane has athickness, the end of the vane also has a radius (i.e. is rounded), andthe exact contact point between the vane and the wall of the cavityvaries slightly with the rotation of the rotor. Since both ends of thevane have the same radius of curvature, this imprecision is equal oneach side, and the exact shape of the cardioid cavity can be adjusted tocompensate and still maintain contact at all points between the vane andthe cavity wall.

With reference now to FIG. 15C, the shaft 730 protrudes below the rotor722 and is fitted with three wheels 772, 774, and 776 which cooperatewith the pump drive mechanism housed in the reusable control unit 404(FIG. 9), which imparts rotational motion to the shaft and thence to therotor. The top most wheel 772 is a smooth alignment wheel, the middlewheel 774 is a toothed driven wheel, and the bottom most wheel 776 isanother smooth alignment wheel. The driven wheel 774 can be constructed,for example, of a plastic material such as nylon, polyurethane or PPS.The alignment wheels 772 and 776 can be constructed, for example, of apolycarbonate material. These three wheels cooperate with a plurality ofwheels on the reusable control unit 404, two of which are depicted inFIG. 9 as guide wheels 410. A toothed drive wheel 408 is driven by thepump drive mechanism 406, and is shown in FIGS. 17A and 17B, whichdepict placement of the pump wheels 772, 774, and 776 within the controlunit 404. FIG. 17A also shows placement of a gear shield 778, whichcovers the receiving opening 402 in the control unit 404 (FIG. 9) oncethe heat exchange cassette 400 b is positioned in place.

When the heat exchange cassette 400 b is inserted into the reusablecontrol unit 404, the toothed driven wheel 774 engages the toothedportion 780 of motor wheel 708. The driven wheel 774 and motor wheel 408are held engaged by contact between guide wheels 410 and alignmentwheels 772, 776. As can be seen in FIG. 17B, the guide wheels 410 have alarger diameter top and bottom sections 782 a, 782 b, respectively, witha small diameter middle section 784. This allows the top sections 782 ato fit snugly against alignment wheel 772 and the bottom sections 782 bto fit snugly against alignment wheel 776, while at the same time themiddle section 784 will not come in to contact with the toothed drivewheel 774. The guide wheels can be machined as a single spool-shapedunit or the top, middle and bottom sections can be separate pieces thatare permanently affixed together. The toothed motor wheel can also bedesigned to have a slightly larger top section 786 a that fits snuglyagainst alignment wheel 772 and/or a slightly larger bottom section 786b that fits snugly against alignment wheel 776. Preferably the motorwheel makes contact with at least one of the smooth alignment wheels.The positioning of the alignment and guide wheels causes the teeth ofmotor wheel 408 and driven wheel 774 to mesh at the appropriate distanceso that the teeth are not forced tightly together. The diameter of thesmooth alignment wheels 772, 776 will be approximately the pitchdiameter of the driven wheel 774 to provide proper positioning of thedrive teeth. Similarly, the diameter of the top and bottom sections, 786a, 786 b, of the motor wheel 408 will be approximately the pitchdiameter of the toothed portion 780 of the motor wheel 408. This isadvantageous in imparting smooth rotational motion without impartingside forces to the drive shaft, or causing friction between the teeth byvirtue of their being jammed together.

The diametral pitch of the driven wheel 774 and the motor wheel 408 arethe same and they preferably will have the same diameter. However theymay be different diameters, but it is preferable that the gear pitch isthe same, for example, a diametral pitch of 48 (48 teeth per inch indiameter) has been found to provide adequate strength with minimal noiseduring operation. A typical driven wheel 774 will have a pitch diameterof 2.54 cm.(1 inch), and the corresponding motor wheel 780 will alsohave a pitch diameter of about 2.54 cm (1 inch).

Methods for Priming the Heat Exchange Catheter System

Referring to FIGS. 18A-18C, several methods of supplying heat exchangefluid to an intravascular heat exchange catheter are illustrated byfluid flow pathways, each pathway illustrating a different embodiment ofthe heat exchange cassette of the invention. In these embodiments, fluidflows from the pump to the heat exchange catheter, returns from thecatheter and passes through the external heat exchanger, and then entersa fluid reservoir. From the reservoir, the fluid moves to the pump, andthe cycle repeats for the desired duration. An optional pressureregulator can be position in the fluid path moving from the pump to thecatheter. Fluid is provided from an external fluid source, which in theembodiment of FIG. 18A enters the priming valve, and in the embodimentsof the FIGS. 18B and 18C directly enters the pump head (of course, asindicated in FIG. 10B, the external source of fluid may be connected tothe reservoir).

Examples of these methods and the respective fluid pathways are furtherunderstood by reference to FIGS. 10A and 13A. In general, the methodcomprises the steps of:

(a) providing power to operate a pump head;

(b) transferring fluid from an external fluid source to a chamber;

(c) pumping fluid from the chamber into a pump cavity;

(d) pumping fluid from the pump cavity to the catheter;

(e) pumping fluid from the catheter to a external heat exchanger whichis positioned in heat transfer relationship with a heater/cooler;

(f) pumping fluid from the external heat exchanger to a heat exchangefluid reservoir;

(g) pumping fluid from the heat exchange fluid reservoir into the pumpcavity; and

(h) repeating steps (d) through (g) for the duration of operation of thecatheter.

The heat exchange cassette of the invention is initially primed, thatis, filled with heat exchange fluid from an external source and excessair removed. This priming of the system of the invention can beaccomplished in numerous ways. One embodiment of the invention utilizesa “valved-priming” mechanism, and is illustrated by the embodiment ofFIGS. 13A-14E. This valved-priming mechanism involves a priming sequencehaving a valve or the like controlling temporary fluid input from anexternal fluid source, and once the system is primed, the valve preventsfurther fluid input from the external source and fluid thereaftercirculates within a closed circuit including the heat exchange cassette400 b and the attached in-dwelling catheter. In the embodiment of FIGS.13A-14E, the valved-priming mechanism 670 is contained within a discreteunit, namely the feedblock section 554. It is understood however, thatthe valved-priming mechanism can be located in another portion of thebulkhead 430 b, for example as part of the pump section 552 or reservoirsection 550, and still serve the same function.

The invention also encompasses a method for automatically commencing andceasing the priming of a heat exchange fluid supply system for supplyinga heat exchange fluid from an external fluid source to an intravascularheat exchange catheter, using the means described above. This methodcomprises the steps of:

(a) first providing power to operate the pump, wherein the reservoir isnot filled to capacity and the valve is in its first position and thepump operates to pump fluid:

a. from the external fluid source through the fluid providing line intothe fill port of the chamber and out of the fluid outlet into the pumpcavity

b. from the pump cavity to the fluid return line to the catheter;

c. from the catheter through the fluid supply line to the external heatexchanger inlet orifice;

d. from the external heat exchanger outlet orifice to the heat exchangefluid reservoir; and

e. into the heat exchange fluid reservoir to fill the reservoir;

(b) then filling the reservoir to capacity; at which point

(c) the optical fluid level detector operates to move the valve to itssecond position and the pump operates to pump fluid from the heatexchange fluid reservoir to the fluid inlet of the chamber and out ofthe fluid outlet into the pump cavity.

When the disposable heat exchange cassette 400 b of the invention isfirst put into operation, the unit is initially filled with heatexchange fluid from an external fluid source such as an IV bag of salineattached to the fill port 632 leading to the fill channel 634. Inaddition, the linear actuator 418 of the valve actuation system 416 isactivated, to place the priming valve 670 in its first position (FIG.14E) with the valve member 676 depressed sufficiently to allow fluid toflow from the IV bag into the valve chamber 636. More specifically,during a priming operation, the push rod 420 in the receiving opening402 of the control unit 404 seen in FIG. 9, passes through the primingvalve aperture 618 in the cover plate 442 b (FIG. 13A) and displaces theflexible membrane 672 downward which, in turn, displaces the valvemember 676 downward, as seen in FIG. 14E. The lower O-ring 692 on thevalve member 676 thus contacts and seals against the floor of the middlesubchamber 682 b, permitting fluid to flow from the fill channel 634into the upper subchamber 682 a, through the middle subchamber 682 b,and through the outlet channel 642 toward the pump head 552. In thismanner, heat exchange fluid from external fluid source 630 (FIG. 13B)enters the feedblock section 554, and then flows into the pump section552. From the pump section 552, the fluid is pumped out through pressureregulating chamber 646, the outlet channel 648 and outlet port 650, andto the catheter inflow line 652.leading to the heat exchange catheter.Fluid is thereafter circulated through the catheter, back through thecatheter inflow line 654 that couples to an inlet port 656 of thefeedblock section 554, through the flow through channel 660 within thepump section 552 leading to a bulkhead outlet 662. Fluid enters andpasses through the external heat exchanger 440 b and back into thereservoir section 550. As the fluid is pumped into the reservoir section550, air displaced by the fluid escapes through the hydrophobic vents588. This generally continues until the system is full of heat exchangefluid and excess air has been vented out of the system. At this point inthe process, the valve 670 is closed from the external fluid source 630(by, e.g., automatic release of the push rod 420) and the fluid supplycircuit between the catheter and the heat exchange cassette 400 b isclosed.

The reservoir section is provided with a means to detect when the fluidreservoir is full, as described below, whereby signals are provided tothe reusable control unit that represent the level of the heat exchangefluid in the reservoir. Using these data, the reusable control unitadjusts the linear actuator 416 so that the position of the valve 670changes and the fluid flow path is altered. Thus when the fluid level inthe reservoir section 550 rises to a sufficient level, a signal is sentto the reusable control unit to deactivate the linear actuator 416 sothat it moves to a released position, thus withdrawing the push rod 420,resulting in the valve member 676 being biased back to its secondposition (FIG. 14D). In this second position, fluid from the now fullreservoir is directed through the feedblock section 554 to the pumpsection 552, while fluid flow from the external fluid source isdiminished or ceases entirely.

In a preferred embodiment the pump would continue to run for a period oftime after the level sensor indicated that the system was full to ensurethat any air bubbles in the catheter or the external heat exchanger orthe bulkhead would be expelled into the reservoir section 550 where theycould vent to the atmosphere. Since the fluid is being drawn from thebottom of the reservoir through reservoir outlet channel 561 (FIG. 13E),and air moves up towards the top of the reservoir where the hydrophobicvents 588 are located, this acts to purge air from the system.Therefore, it is important to realize that the priming valve 670 mayalso have a third position that is an intermediate position from itsfirst and second positions described above. In this manner, heatexchange fluid may enter the central chamber 636 from either thereservoir or the external fluid source, or both simultaneously if thepriming valve 670 is opened to this intermediate position. So, forexample, in an embodiment of the intention that utilizes the pump in afirst, intermediate and then second position, fluid would enter the pumpsolely from the external fluid source (first position, FIG. 14E), thenfluid would enter the pump in part from the external fluid source and inpart from the reservoir section 550 (intermediate position) and finallyfluid would enter the pump solely from the reservoir section 550 (secondposition, FIG. 14D).

It should be noted that priming of the system occurs prior to theinsertion of the heat exchange catheter into the patient, with the heatexchange balloon outside the body. Indeed, the heat exchange balloon isdesirably restrained within a protective tubular sheath, or is otherwiseradially constrained, to prevent inflation thereof during priming. Oncepriming is complete, the pump motor is halted, the protective sheath isremoved, and the catheter is inserted to the desired location within thepatient. The sheath thus ensures a radially compact profile of thecatheter during priming of the system and subsequent intravascularinsertion, which prevents injury and facilitates the insertion so as tospeed up the procedure.

Referring to the embodiment of FIGS. 13-15 and the flow diagram of FIG.18A, a method for supplying heat exchange fluid to an intravascular heatexchange catheter comprises the steps of:

(a) transferring fluid from an external fluid source 630 to a fluidreservoir 550;

(b) providing power to operate a pump head 642;

(c) venting air from the fluid reservoir section 550 as the air isdisplaced by the fluid from the external fluid source;

(d) pumping fluid through a circuit that includes the fluid reservoirsection 550 through a pump cavity 720, to a heat exchange catheter, thento an external heat exchanger 440 b which is positioned in heat transferrelationship with a heater/cooler, and hence the fluid, and airdisplaced by the circulating fluid, flow from the external heatexchanger 440 b to the fluid reservoir 550;

(e) venting the air displaced by the circulating heat exchange fluidfrom the fluid reservoir section 550;

(f) repeating steps (a) through (e) for the duration of operation of thecatheter.

Preferably a step for measuring the fluid level in the heat exchangefluid reservoir is included to insure that the reservoir remains full.Such a step can also comprise using an optical fluid level detector todetermine the fluid level, where step (h) begins when the reservoir isfilled to capacity and step (b) ceases when step (h) begins. The methodfor supplying heat exchange fluid to a catheter for the embodiment ofFIG. 10A uses a passive-priming mechanism, while the method for theembodiment of FIG. 13A uses a unique valved-priming mechanism, describedin detail above. In the priming mechanism shown in FIG. 10A, the fluidlevel measuring step may also comprise using an optical fluid leveldetector to determine the fluid level, where step (g) begins when thereservoir is filled to capacity and step (b) ceases when step (g)begins.

More particularly, the embodiment of FIGS. 10A-10D provides themechanism for passively priming the system with heat exchange fluid froman external source 454. The external fluid source 454 is generally hungor placed at a location above the reservoir 450, and is connected by afluid providing line 456 to the reservoir. The reservoir 450 has a fillport 476 connected to the fluid providing line 456, and thus fluid flowsinto the reservoir 450 which communicates with the pump section 452,thus priming the pump head 490. Initially, with the catheter out of thepatient's body and sheathed, the pump is operated to draw heat transferfluid from the external fluid supply and circulate it through thesystem. The air that is in the system is vented through the hydrophobicair vents. When the pressure in the system is equal to the head pressurefrom the external fluid source (this will happen at a level whichdepends on the pump pressure and the height of the external fluid sourceabove the reservoir) the system will essentially be in equilibrium andwill cease drawing fluid from the external source. At this point thecatheter and heat exchange cassette system will be considered to beprimed. The heat exchange catheter will generally thereafter be insertedinto the patient, and as the system is operated, any fluid required tobe added to the system to maintain the pressure equilibrium mentionedabove will be drawn from the external source which is in fluidcommunication with the reservoir through fluid providing line. Likewise,any buildup of pressure in the system due, for example to the heatingand expanding of the system, will be relieved by fluid flowing back intothe external fluid supply source 454. Because of the ability of thesystem to react to minor expansions and contractions of fluid supply,there is no need to monitor the high level of fluid, and only redundantsensors of the low level need be incorporated into the heat exchangecassette. This has the advantage of automatic maintaining a relativelyuniform fluid level without the need for sensors and the like.

Safety Systems

The reservoir section can be provided with a means to monitor the amountof heat exchange fluid that is in the system, more specifically anoptical means for detecting the level of fluid contained within thefluid reservoir. Since the heat exchange fluid is a biocompatible fluidand the volume of the external source is only about 250 ml, it is notexpected that fluid leakage into the patient will be problematic. Itwould be undesirable, however, to have the fluid level fall so low thatair is pumped into a patient. Therefore the heat exchange fluid supplysystem of the invention is designed to detect the level of the fluid inthe system so that a warning or other measure can be instituted if thesystem becomes unacceptably low. In a preferred embodiment, two prismsin the bulkhead reservoirs, each having a corresponding beam source andbeam, are utilized. Each prism will have a corresponding beam source andsensor mounted on the reusable control unit at a location adjacent tothe prism.

For example, FIG. 9 illustrates placement of an optical beam source 412and optical beam sensor 414 for the first prism 590 a in the bulkheaddesign of FIGS. 13A-13E. As seen in FIG. 13E, the transparent window 591configured in the end of the reservoir container 580 allows for opticalobservation of the fluid level in the reservoir cavity 584. An adjacentbeam source and sensor would also be provided for the second prism 590b, if present.

For the bulkhead design of FIG. 10A, the beam source(s) and sensor(s)would be positioned on the control unit 404 at a location underneath thefirst and second prisms 486 a, 486 b. For example, the fluid levelmeasurement sensor module 276 mounted on the underside of the lowerguide assembly 266 in FIG. 6B may include optical transmitters/sensorsthat are placed in registry with the transparent window 316 so as tointeract with the heat exchange cassette and provide an indication offluid level within the unit. The prisms have a diffraction surface andmay be machined separately using a material such as polycarbonate andthen affixed within the reservoir section, or they may be machined aspart of the section. Again, although only one prism is needed for thefluid level detection method to function, it may be desirable to includea second redundant prism described below.

The second prism/source/sensor is redundant and functions to monitor thesame fluid level as the first prism but operates as a safety mechanismin the even the first prism/source/sensor fails to function properly.Alternatively, one of the prisms may also have a “high level” sensingsystem that can be used to signal the control unit when the fluid in thereservoir reaches a certain high level. This is useful, for example,when the valved-priming system is used and detection of a high or fulllevel is needed to determine when to activate the valve to stop thepriming sequence. If desired, both high level and low level sensors canbe employed on each prism. The sensors will generate a signal indicatingthat either there is or is not fluid at the level of the optical beam.If the optical beam source and sensor are positioned or the optical beamis directed near the top of the tank, the indication that the fluid hasreached that level will trigger the appropriate response from thecontrol system, for example to terminate a fill sequence. On the otherhand, if the sensor is positioned or optical beam directed to sense thefluid level on the bottom of the tank, then the fluid level detector isconfigured to detect a low fluid level and can generates a signalrepresenting such low level. The heat exchange cassette can then beconfigured to respond to this signal indicative of a low level of fluidin the reservoir. For example, the pump head can be designed to beresponsive to this signal such that the pump head stops pumping when alow fluid level is detected, so that air will not be pumped into theheat exchange catheter. In addition, an alarm may sound and an alarmdisplay, such as the display 200 of FIG. 5C, may be activated to alertthe operator to the low fluid level condition.

In a preferred embodiment of the present invention, several levels ofsafety redundancy are provided to prevent failure of the system, andpotential injury to the patient. First, two microprocessors may beprovided and constantly monitored for agreement. If one fails, thesystem alarms and shuts. Secondly, two or more patient sensors may beprovided and monitored for agreement. They are sampled frequently by thecontroller and if the values do not agree, as with the microprocessor,the system alarms and shuts down. Likewise, two or more fluid levelsensors for the heat exchange circulation path desirably agree forredundancy. Still further, two or more temperature sensors for the heatexchange medium could be provided and monitored for agreement. In short,various redundant subsystems of the overall system ensure properoperation and the feedback therefrom is used to shut off the system ifnecessary.

In a preferred embodiment of the invention, the reservoir section isprovided with a means to detect when the fluid reservoir is too low.Typically, an optical beam source would begin operation after thereservoir fills with fluid. In operation, the optical beam sourceproduces an optical beam that is directed into the prism from the bottomand is internally reflected one or more times within the prism at itssurface interface with the fluid and back to the optical beam sensor. Aslong as fluid is in the reservoir, the sensor will observe a reflectedlight beam and the pump will continue to operate, moving fluid throughthe heat exchange cassette and catheter. However, if the fluid leveldrops below the upper reflective surfaces of the prism, thus changingthe reflective index at that internal surface, the sensor then will notobserve a reflected light beam. When no such reflected beam is received,the system sounds an alarm and ceases to pump.

In the embodiment of the invention that involves a valved-primingsequence, the optical beam source is turned on to produce an opticalbeam that is directed towards the top of the prism. The prism isconfigured to reflect the beam if the top surface is covered with theheat exchange fluid. A sensor is located below the prism where the lightbeam will be reflected from the top surface of the prism. As long as thesensor below does observes a reflected light beam, the fill or primingoperation of the heat exchange cassette continues to run. As the fluidlevel rises, at some point it reaches a level such that the top surfaceof the prism is covered with the fluid, and the optical beam reflectedback to the sensor. When the sensor observes a reflected light beam, itgenerates a signal to the controller to cease the priming operation ofthe heat exchange cassette, for example by activating a motor towithdraw the push rod 420. Thereafter, the fluid level detector operatesto detect a low level for safety purposes, that is once the presence ofa signal indicates that the priming has been completed, the sensorcontinues to generates a signal indicating that the fluid level is abovethe prism. When the fluid level falls below the reflecting surface ofthe prism, the sensor sends a signal to the controller that will thenact to trigger an alarm and shut down the fluid flow. In this way thesystem may automatically prime, subsequently be automatically signaledto run, and then automatically shut down if the fluid level falls.

Additional safety systems that are contemplated by the invention includebubble detectors at various locations on the conduits to detect anybubble that may be pumped into the fluid system and temperature monitorsthat may signal if a portion of the system, or the fluid, is at atemperature that is unacceptably high or low. A detector to indicatewhether the fluid sensor optical beam sources are operational may besupplied, for example by placing a detector located to detect theoptical beam initially when the system is turned on but there isinsufficient fluid in the reservoir to cause the beam to diffract backto the detector. The control unit depicted in FIGS. 1,2 and 5 providefor multiple patient temperature sensors. A warning may sound, and thesystem may shut down, if the temperature signal from the two differentsensors are dramatically different, indicating that one of the sensors,perhaps the one driving the control of the system, is misplaced, is notfunctioning, has fallen out or the like. Other similar safety andwarning systems are contemplated within the scope of the system of theinvention.

It should also be understood, in accordance with the present invention,that the controller processor may be configured to simultaneouslyrespond to multiple sensors, or to activate or de-activate variouscomponents such as several heat exchangers. In this way, for example, acontroller might heat blood that is subsequently circulated to the corebody in response to a sensed core body temperature that is below atarget temperature for the core, and simultaneously activate a secondheat exchanger to cool blood that is directed to the brain region inresponse to a sensed brain temperature that is above a targettemperature for the brain. It may be that the sensed body temperature isat the target temperature and thus the heat exchanger that is in contactwith blood circulating to the body core may be turned off by thecontroller, while at the same time the controller continues to activatethe second heat exchanger to cool blood that is directed to the brainregion. Any of the many control schemes that may be anticipated by anoperator and programmed into the control unit are contemplated by thisinvention.

A further advantage of the system of the present invention is that allof the portions of the system that are in contact with the patient aredisposable, but substantial and relatively expensive portions of thesystem are reusable. Thus, the catheter, the flow path for sterile heatexchange fluid, the sterile heat exchange fluid itself, and the pumphead are all disposable. Even if a rupture in the heat exchange balloonpermits the heat exchange fluid channels and thus the pump head to comein contact with a patient's blood, no cross-contamination will occurbetween patients because all those elements are disposable. The pumpdriver, the electronic control mechanisms, the thermoelectric cooler,and the manual input unit, however, are all reusable for economy andconvenience. Desirably, as illustrated, all of these re-usablecomponents are housed within a single control unit. Likewise, thevarious sensors distributed around body and along the catheter may bedisposable, but the controller processor to which they attach isre-usable without the need for sterilization.

It will also be appreciated by those of skill in the art that the systemdescribed herein may be employed using numerous substitutions,deletions, and alternatives without deviating from the spirit of theinvention as claimed below. For example, but not by way of limitation,the serpentine pathway in the heat exchange plate may be a coil or othersuitable configuration, or the sensors may sense a wide variety of bodylocations and other parameters may be provided to the processor, such astemperature or pressure. Further, the in-dwelling heat exchanger at theend of the catheter may be any appropriate type, such as a non-balloonheating/cooling element. An appropriate pump might be provided that is ascrew pump, a gear pump, a diaphragm pump, a peristaltic roller pump, orany other suitable means for pumping the heat exchange fluid. All ofthese and other substitutions obvious to those of skill in the art arecontemplated by this invention.

While particular embodiments of the invention have been described above,for purposes of or illustration, it will be evident to those skilled inthe art that numerous variations of the above-described embodiments maybe made without departing from the invention as defined in the appendedclaims.

What is claimed is:
 1. A controller for controlling the temperature andflow of a heat exchange fluid within a circuit, comprising: a heatexchange catheter insertable within a patient, the catheter configuredto heat or cool blood flowing past the catheter within the patient; anexternal heat exchanger; a pump for flowing heat exchange fluid throughthe circuit; a thermoelectric heating and/or cooling element, thethermoelectric heating and/or cooling element being in non-fluid thermalcontact with the external heat exchanger containing the heat exchangefluid; a patient sensor positioned and configured to generate a signalrepresenting a biophysical condition of a patient; a microprocessorconnected to receive the signal from the patient sensor and beingresponsive to the signal to control the thermoelectric heating and/orcooling element; a mechanical drive unit for activating the pumpcontained in the circuit; and a safety sensor for detecting a fluidparameter representing the presence of air in the circuit and generatinga safety signal representative of the presence or absence of the fluidparameter, the safety signal being transmitted to the microprocessorthat responds by controlling the flow of heat exchange fluid within thecircuit.
 2. The controller of claim 1, wherein the safety sensor furthercomprises an optical fluid level detector positioned to optically sensethe fluid level within the circuit.
 3. The controller of claim 2 whereinthe optical fluid level detector includes an optical beam source and anoptical sensor, wherein the optical beam source and optical sensor arepositioned adjacent the circuit to sense the level of fluid therein. 4.The controller of claim 1 further comprising a plurality of the patientsensors for sensing biophysical conditions of a patient, themicroprocessor being responsive to each of the sensors to control thegenerating element.
 5. The controller of claim 4, wherein themicroprocessor is configured to compare the signals from at least two ofthe plurality of patient sensors and produce an alarm condition when thesignals do not agree.
 6. The controller of claim 1 wherein themicroprocessor further receives a target temperature input, and thesignal represents a sensed patient temperature, the microprocessor isconfigured to add heat to the fluid if the target temperature is abovethe patient temperature and remove heat from the fluid if the targettemperature is below the patient temperature, and wherein themicroprocessor responds to the signal from the patient sensor with aproportional integrated differential (PID) response such that the rateat which patient temperature approaches the target temperature iscontrolled.
 7. A controller for controlling the temperature and flow ofa heat exchange fluid within a circuit, comprising: a heat exchangecatheter insertable within a patient, the catheter configured to heat orcool blood flowing past the catheter within the patient; an externalheat exchanger; a pump for flowing heat exchange fluid through thecircuit; a thermoelectric heating and/or cooling element, thethermoelectric heating and/or cooling element being in non-fluid thermalcontact with the external heat exchanger containing the heat exchangefluid; a patient sensor positioned and configured to generate a signalrepresenting a biophysical condition of a patient; a microprocessorconnected to receive the signal from the patient sensor and beingresponsive to the signal to control the thermoelectric heating and/orcooling element; a mechanical drive unit for activating the pumpcontained in the circuit; and a bubble detector for detecting gasentrained in the heat exchange fluid, and for generating a safety signalrepresenting the presence of bubbles within the circuit, the safetysignal being transmitted to the microprocessor that responds bycontrolling the flow of heat exchange fluid within the circuit.
 8. Acontroller for controlling the temperature and flow of a heat exchangefluid within a circuit, comprising: a heat exchange catheter insertablewithin a patient, the catheter configured to heat or cool blood flowingpast the catheter within the patient; an external heat exchanger; a pumpfor flowing heat exchange fluid through the circuit; a thermoelectricheating and/or cooling element, the thermoelectric heating and/orcooling element being in non-fluid thermal contact with the externalheat exchanger containing the heat exchange fluid; a mechanical driveunit for activating the pump contained in the circuit for pumping theheat exchange fluid; a microprocessor connected to control both thethermoelectric heating and/or cooling element and the mechanical driveunit; and a safety system for detecting problems in the circuit, thesafety system including a plurality of sensors that generate signalsindicative of respective parameters of the system and/or patient, atleast one of the sensors for detecting the presence of air in the heatexchange fluid, the signals being transmitted to the microprocessor thatresponds by controlling the flow of the heat exchange fluid within thecircuit.
 9. The controller of claim 8, wherein the safety systemincludes a sensor for detecting the fluid level within the circuit. 10.The controller of claim 8, wherein the safety system includes a sensorfor detecting the temperature of a location within the patient.
 11. Thecontroller of claim 10, further including a redundant sensor fordetecting the temperature of a location within the patient, themicroprocessor being responsive to a difference in the temperaturessensed by the sensor and the redundant sensor.
 12. A controller forcontrolling the temperature and flow of a heat exchange fluid within acircuit, comprising: a heat exchange catheter insertable within apatient, the catheter configured to heat or cool blood flowing past thecatheter within the patient; an external heat exchanger; a pump forflowing heat exchange fluid through the circuit; a thermoelectricheating and/or cooling element, the thermoelectric heating and/orcooling element being in non-fluid thermal contact with the externalheat exchanger containing the heat exchange fluid; a mechanical driveunit for activating the pump contained in the circuit for pumping theheat exchange fluid; a microprocessor connected to control both thethermoelectric heating and/or cooling element and the mechanical driveunit; and a safety system for detecting problems in the circuit, thesafety system including a plurality of sensors that generate signalsindicative of respective parameters of the system and/or patient, atleast one of the sensors for detecting bubbles within the circuit, thesignals being transmitted to the microprocessor that responds bycontrolling the flow of the heat exchange fluid within the circuit. 13.A controller for controlling the temperature and flow of a heat exchangefluid within a circuit, the circuit comprising a heat exchange catheterinsertable within a patient, an external heat exchanger, and a pump forflowing heat exchange fluid through the circuit, the controllercomprising: a heat and/or cold generating element, the generatingelement being in thermal contact with the external heat exchangercontaining the heat exchange fluid; a mechanical drive unit foractivating the pump contained in the circuit for pumping the heatexchange fluid; a microprocessor connected to control both thegenerating element and the mechanical drive unit; and a safety systemfor detecting problems in the circuit, the safety system including aplurality of sensors that generate signals indicative of respectiveparameters of the system and/or patient, the signals being transmittedto the microprocessor that responds by controlling the operation of thegenerating element and the mechanical drive unit, wherein the safetysystem includes a sensor for detecting the operating status of thegenerating element.
 14. A controller for controlling the temperature andflow of a heat exchange fluid within a circuit, the circuit comprising aheat exchange catheter insertable within a patient, an external heatexchanger, and a pump for flowing heat exchange fluid through thecircuit, the controller comprising: a heat and/or cold generatingelement, the generating element being in thermal contact with theexternal heat exchanger containing the heat exchange fluid; a mechanicaldrive unit for activating the pump contained in the circuit for pumpingthe heat exchange fluid; a microprocessor connected to control both thegenerating element and the mechanical drive unit; and a safety systemfor detecting problems in the circuit, the safety system including aplurality of sensors that generate signals indicative of respectiveparameters of the system and/or patient, the signals being transmittedto the microprocessor that responds by controlling the operation of thegenerating element and the mechanical drive unit, wherein the safetysystem includes a sensor for detecting the operating status of themechanical drive unit.